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At least 163 records · Page 9Linked to original sources
PubMed2003

Valveless pumping in a fluid-filled closed elastic tube-system: one-dimensional theory with experimental validation.

An elastic rubber tube is connected with a stiffer rubber tube forming two halves of a torus and filled with water. Compressing one of the rubber tubes symmetrically and periodic at a point of asymmetry creates a remarkable unidirectional mean flow in the system. The size and the direction of the mean flow depend on the frequency of compression, the elasticity of the tubes, the compression ratio, and the type of compression with respect to time in a complicated manner. The system is modelled using a one-dimensional theory derived by averaging the Navier-Stokes equations ignoring higher order terms in a certain small quantity. The one-dimensional model is analysed partly analytically and partly numerically. A series of experiments on a physical realisation of the system are described. The theoretical findings and experimental results are compared; They show a remarkable agreement between the experiments and the predictions of the model. Frequencies at which the mean flow change direction are predicted numerically as well as analytically and the two results are compared.

Blood Flow Velocity↗
PubMedDate not supplied

Experimental validation of a glucose-insulin control model to stimulate patterns in glucose turnover.

To verify a structured model of the glucose-insulin system, metabolic measurements were compared with model-based simulations in insulin-dependent diabetic dogs which had been previously identified in terms of model parameters. Glycaemia, glucosuria, plasma insulin, and the rates of appearance Ra and disappearance Rd of glucose (kinetics of double-labelled glucose, evaluated according to Steele's equation in its non-steady-state version) were observed under the following conditions, starting from normoglycaemia during glucose-controlled insulin infusion (GCII): (I) insulin withdrawal, (II) insulin withdrawal and glucose infusion, (III) constant i.v. infusion of glucose and insulin, (IV) glucose infusion during GCII. After fitting the patterns of glycaemia, simulations of the other state variables were accomplished, employing the individual model parameters, the preset experimental inputs, and the GCII control constants (test IV only). Under nearly all conditions, correspondence was excellent between measured and simulated data. There were, however, the following exceptions: incomplete representation by the model of kinetics in glucose utilisation after interruption of insulin supply, overestimation of glucosuria by the model in the presence of insulin. It is concluded that the model provides a reasonable representation of metabolic processes which are of importance in the treatment of insulin-dependent diabetes mellitus and that it might thus appropriately simulate the outcome of metabolic regimens.

Absorption↗
PubMedDate not supplied

Kinetic modelling as a tool for the design of a vascular bioartificial pancreas: feedback between modelling and experimental validation.

A bioartificial pancreas is a system which contains isolated islets of Langerhans protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to lymphocytes and immunoglobulins. However, it is necessary to design a device which performs as a closed-loop insulin delivery system, more specifically which rapidly responds to a change in the recipient's blood glucose concentration by an appropriate change in insulin release. We have designed a system intended to be connected as an arteriovenous shunt of the recipient; islets are placed between two flat ultrafiltration membranes, and blood circulates successively above the upper, and below the lower, membrane, in reverse direction. A complete kinetic model of glucose transfer from blood to the islet compartment, of insulin generation by the islets displaying a biphasic insulin pattern, and of insulin transfer into the bloodstream was described, and parameters were calculated on the basis of experimental data obtained when islets of Langerhans were perfused in vitro with a synthetic buffer. The resulting calculations indicated that both diffusional and convective transfers were involved in glucose and insulin mass transfer across the membrane, the contribution of diffusion being the most important. The geometry of the system was therefore modified in order to decrease the resistance to flow inside the blood channel. This should increase, at a given hydrostatic pressure, the blood flow rate, and thereby improve the diffusional transfer of insulin. This should also decrease the thrombogenicity of the device.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Experimental validation of the Wigner distributions theory of phase-contrast imaging.

Recently, a new theory of phase-contrast imaging has been proposed by Wu and Liu [Med. Phys. 31, 2378-2384 (2004)]. This theory, based upon Wigner distributions, provides a much stronger foundation for the evaluation of phase-contrast imaging systems than did the prior theories based upon Fresnel-Kirchhoff diffraction theory. In this paper, we compare results of measurements made in our laboratory of phase contrast for different geometries and tube voltages to the predictions of the Wu and Liu model. In our previous publications, we have used an empirical measurement (the edge enhancement index) to parametrize the degree of phase-contrast effects in an image. While the Wu and Liu model itself does not predict image contrast, it does measure the degree of phase contrast that the system can image for a given spatial frequency. We have found that our previously published experimental results relating phase-contrast effects to geometry and x-ray tube voltage are consistent with the predictions of the Wu and Liu model.

Algorithms↗
PubMed2002

Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods.

We report here the identification of a previously unknown transcription regulatory element for heat shock (HS) genes in Caenorhabditis elegans. We monitored the expression pattern of 11,917 genes from C. elegans to determine the genes that were up-regulated on HS. Twenty eight genes were observed to be consistently up-regulated in several different repetitions of the experiments. We analyzed the upstream regions of these genes using computational DNA pattern recognition methods. Two potential cis-regulatory motifs were identified in this way. One of these motifs (TTCTAGAA) was the DNA binding motif for the heat shock factor (HSF), whereas the other (GGGTGTC) was previously unreported in the literature. We determined the significance of these motifs for the HS genes using different statistical tests and parameters. Comparative sequence analysis of orthologous HS genes from C. elegans and Caenorhabditis briggsae indicated that the identified DNA regulatory motifs are conserved across related species. The role of the identified DNA sites in regulation of HS genes was tested by in vitro mutagenesis of a green fluorescent protein (GFP) reporter transgene driven by the C. elegans hsp-16-2 promoter. DNA sites corresponding to both motifs are shown to play a significant role in up-regulation of the hsp-16-2 gene on HS. This is one of the rare instances in which a novel regulatory element, identified using computational methods, is shown to be biologically active. The contributions of individual sites toward induction of transcription on HS are nonadditive, which indicates interaction and cross-talk between the sites, possibly through the transcription factors (TFs) binding to these sites.

Animals↗
PubMed1995

Impact of electroosmosis on isotachophoresis in open-tubular fused-silica capillaries: analysis of the evolution of a stationary steady-state zone structure by computer simulation and experimental validation.

A dynamic computer model for simulation of open-tubular capillary electrophoresis that includes in situ calculation of electroosmosis along the fused-silica capillary column has been applied to the characterization of an anionic isotachophoretic system in presence of a cathodic electroosmotic flow. For each column segment, electroosmosis is calculated with the use of a wall mobility, the voltage gradient and the degree of dissociation of the silanol surface groups of the capillary wall. Then, the bulk capillary flow is taken to be the average of all of the segment flows and considered to represent a plug flow. This simple approach enables the combined simulation of the temporal behavior of an isotachophoretic zone structure in presence of electroosmosis. For a model anionic isotachophoretic configuration at pH 6, simulation data reveal the asymptotic formation of a stationary steady-state zone configuration in which electrophoretic and electroosmotic zone displacements are opposite and of equal magnitude. The position of the stationary boundaries are predicted to be dependent on the selected wall pK and mobility values. For two different instruments, qualitative agreement between experimental data and simulation results obtained with a wall pK between 5 and 6 is demonstrated. However, for the two experimental setups, significant differences in electroosmotic pumping (i.e. wall mobility values) are noted.

Anions↗
PubMed2002

[The active site of human glucocerebrosidase: structural predictions and experimental validations].

Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase which cleaves the beta-glucosidic linkage of glucosylceramide, a normal intermediate in glycolipid metabolism. Glucocerebrosidase belongs to the clan GH-A of glycoside hydrolases, a large group of enzymes which function with retention of the anomeric configuration at the hydrolysis site. Accurate three-dimensional (3D) structure data for glucocerebrosidase should help to better understand the molecular bases of Gaucher disease. As such 3D structure data were not available, we used the two-dimensional hydrophobic cluster analysis (HCA) method to make structure predictions for the catalytic domains of clan GH-A glycoside hydrolases. We found that all the enzymes of clan GH-A may share a similar catalytic domain consisting of an (alpha/beta)8 barrel with the critical acid/base and nucleophile residues located at the C-terminal ends of strands beta 4 and beta 7, respectively. In the case of glucocerebrosidase, Glu 235 was predicted to be the putative acid/base catalyst whereas the nucleophile was located at Glu 340. Next, in order to obtain experimental evidence supporting these HCA-based predictions, we used retroviral vectors to express, in murine null cells, E235A and E340A mutant proteins, in which alanine residues unable to participate in the enzymatic reaction replace the presumed critical glutamic acid residues. Both mutants were found to be catalytically inactive although they were correctly folded/processed and sorted to the lysosome. Thus, Glu 235 and Glu 340 do indeed play key roles in the active site of human glucocerebrosidase as predicted by the HCA analysis. In a broader perspective, our work points out that bioinformatics approaches may be highly useful for generating structure-function predictions based on sequence-structure interrelationships, especially in the context of a rapid increase in protein sequence information through genome sequencing.

Amino Acid Sequence↗
PubMed1993

[The experimental validation of the clinical use of new surgical lasers].

A comparative evaluation has been carried out between the effects of surgical CO2-laser (lambda = 10.6 mcm) and lasers previously unused in medicine: Yag-erbium (lambda = 2.94 mcm) and YAG-erbium-in-glass lasers on biological tissue. The cutting properties of the lasers, nature of their effect on tissue and the period of healing of laser injury were studied morphologically. Effects of radiation on the energetic, biosynthetic and proliferative processes in the liver tissue, as well as the activity of transamination enzymes have been investigated. It has been shown that laser radiation of lambda = 1.54 and lambda = 2.94 mcm can destroy biological tissue with minimum inflammatory reaction as compared to CO2-laser. It has been ascertained that better marked changes in bioenergetics, aminotransferase activity, RNA and DNA contents are observed under the influence of CO2 and YAG-erbium lasers. Exposure of liver to YAG-erbium-in-glass laser radiation produced minimum changes in cells of the tissue contiguous to the injury. Thus, under its influence the majority of the investigated indices either changed insignificantly or improved. This might account for a positive effect of this laser on the dynamics and quality of the injury healing. The experimental studies gave basis for creation of working models of laser devices (lambda = 1.54 mcm) which are undergoing successful clinical trials at present.

Animals↗
PubMed2003

Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis.

Real-time PCR is being used increasingly as the method of choice for mRNA quantification, allowing rapid analysis of gene expression from low quantities of starting template. Despite a wide range of approaches, the same principles underlie all data analysis, with standard approaches broadly classified as either absolute or relative. In this study we use a variety of absolute and relative approaches of data analysis to investigate nocturnal c-fos expression in wild-type and retinally degenerate mice. In addition, we apply a simple algorithm to calculate the amplification efficiency of every sample from its amplification profile. We confirm that nocturnal c-fos expression in the rodent eye originates from the photoreceptor layer, with around a 5-fold reduction in nocturnal c-fos expression in mice lacking rods and cones. Furthermore, we illustrate that differences in the results obtained from absolute and relative approaches are underpinned by differences in the calculated PCR efficiency. By calculating the amplification efficiency from the samples under analysis, comparable results may be obtained without the need for standard curves. We have automated this method to provide a means of streamlining the real-time PCR process, enabling analysis of experimental samples based upon their own reaction kinetics rather than those of artificial standards.

Actins↗
PubMed1988

[Experimental validation and the initial experience of the use of intravenous laser irradiation of the blood in oncology].

The treatment of some non-oncological and then oncological patients was undertaken on the basis of the results obtained by laser blood irradiation (a helium-neon laser, the wavelength of 0.633 micron) in the tumour-bearing mice. The method was applied to 25 patients with the cancer of cervix uteri after their radiotherapy and resulted in the stimulation of their hemopoietic and immunologic systems.

Animals↗
PubMed1997

Elastic work of breathing during continuous positive airway pressure in intubated patients with chronic obstructive pulmonary disease (theoretical analysis and experimental validation).

BACKGROUND: Continuous positive airway pressure (CPAP) is known to decrease inspiratory work of breathing in patients with chronic obstructive pulmonary disease (COPD). This effect is primarily attributed to a reduction in inspiratory elastic work of breathing (Wi,el) related to a decrease in intrinsic positive end-expiratory pressure (PEEP). METHODS: The aim of this study is to design a model for computation of Wi,el on the basis of respiratory mechanics in patients with COPD, at various intrinsic PEEP- and CPAP-levels. The model was used to estimate the optimal CPAP-level with respect to the intrinsic PEEP-level in terms of reduction of Wi,el. Calculations of the decrease in Wi,el due to CPAP obtained with the model were compared to changes in Wi,el and total work of breathing (Wi,tot) determined from respiratory measurements in patients with COPD. RESULTS: Model calculations revealed that Wi,el was minimal whenever a CPAP-level equal to the intrinsic PEEP-level was applied. When a CPAP-level exceeding the intrinsic PEEP-level was applied, the reduction in Wi,el was less. Comparing these results to the respiratory measurements, a similar pattern in reduction of Wi,el and Wi,tot was established, although absolute values of the differences were smaller in the experimental data. CONCLUSION: This study indicates that in order to reduce Wi,el in patients with COPD, intrinsic PEEP should be measured and the CPAP-level adjusted to the intrinsic PEEP-level.

Aged↗
PubMed2002

Experimental validation of Gaussian-3 lithium cation affinities of amides: implications for the gas-phase lithium cation basicity scale.

Using a refined Gaussian-3 (G3) protocol, the highest level of ab initio calculations reported so far, we have established the Li+ cation binding enthalpy (affinity) at 0 K (in kJ mol-1) for formamide (195.7), N-methylformamide (209.2), N,N'-dimethylformamide (220.0), acetamide (211.7), N-methylacetamide (222.5), and N,N'-dimethylacetamide (230.1), with an estimated maximum uncertainty of +/-8 kJ mol-1. With these six theoretical lithium cation binding affinities as reference values, the absolute Li+ affinities of imidazole and dimethoxyethane were determined by the extended kinetic method, and by adopting the statistical data treatment protocol recently proposed by Armentrout. The Li+ affinities obtained for these two ligands are in good agreement (within 6 kJ mol-1) with recent values determined by the threshold collision-induced dissociation method, and consistent with the Li+ basicity values first reported by Taft and co-workers in 1990. Our study confirms that the previously suggested, and recently implemented, downward revision of Taft's original basicity scale by 10.9 kJ mol-1 is justified for ligands with revised basicities less than 151 kJ mol-1. However, for selected ligands with Li+ basicities greater than 151 kJ mol-1, including some of the six amides studied in this work, the reported discrepancy between theoretical and experimental estimates in the revised Li+ basicity scale of Burk et al. is likely to arise from experimental uncertainties.

Algorithms↗
PubMed1993

Experimental validation of geometric and densitometric coronary measurements on the new generation Cardiovascular Angiography Analysis System (CAAS II).

Computer-assisted contour detection and videodensitometric cross sectional area assessment of coronary artery obstructions on the CAAS II system were validated in vitro and in vivo by angiographic cinefilm recording and automated measurement of stenosis phantoms (luminal diameter 0.5, 0.7, 1.0, 1.4, 1.9 mm) which were first inserted in a plexiglass model and then serially implanted in swine coronary arteries. "Obstruction diameter" (OD) and "obstruction area" (OA) values obtained from 10 in vitro and 19 in vivo images at the site of the artificial stenoses were compared with the true phantom dimensions. The in vitro assessment of OD yielded an accuracy of 0.00 +/- 0.11 mm (correlation coefficient: r = 0.98, y = 0.18 + 0.82x, standard error of estimate: SEE = 0.08), whereas the in vivo measurement of OD gave an accuracy of -0.01 +/- 0.18 mm (r = 0.94, y = 0.22 + 0.82x, SEE = 0.15). The assessment of OA gave an accuracy of -0.08 +/- 0.21 mm2 in vitro (r = 0.97, y = 0.08 + 0.99x, SEE = 0.22) and -0.22 +/- 0.32 mm2 in vivo (r = 0.95, y = 0.21 + 1.01x, SEE = 0.33). The mean reproducibility was +/- 0.09 mm for geometric measurements and +/- 0.21 mm2 for videodensitometric assessments, respectively. Thus, due to inherent limitations of the imaging chain, the reliability of geometric coronary measurements is still far superior to videodensitometric assessments of vessel cross sectional areas.

Absorptiometry, Photon↗
PubMed2004

Bivalirudin-associated intracoronary thrombosis during gamma-brachytherapy and its experimental validation in acute swine model.

Bivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Cases of intracoronary thrombosis have been reported with beta-radiation when bivalirudin is used as an anticoagulant. We report two cases of intracoronary thrombosis with gamma-radiation when bivalirudin is used.

Aged↗
PubMed1992

An experimentally validated panel of subfamily-specific oligonucleotide primers (V alpha 1-w29/V beta 1-w24) for the study of human T cell receptor variable V gene segment usage by polymerase chain reaction.

We report here the characterization of a series of T cell receptor (TcR) V alpha or V beta subfamily-specific oligonucleotide primers. Criteria that have guided the design of each oligonucleotide include appropriate thermodynamic parameters as well as differential base-pairing scores with related and unrelated target sequences. The specificity of the oligonucleotides for each V alpha or V beta subfamily was tested by polymerase chain reaction (PCR) on both a series of TcR encoding plasmid DNA and clonal T cell populations. Unexpected cross-reactivities were observed with plasmid cDNA sequences corresponding to unrelated subfamily gene segments. This led to the synthesis of additional series of oligonucleotides to obtain a relevant panel. A series of V alpha 1-w29/V beta 1-w24 TcR subfamily-specific oligonucleotides was eventually selected which generates little, if any, cross-reactivity. The use of C alpha or C beta primers for the amplification of internal positive control templates (i.e. C beta for the V alpha series and C alpha for the V beta series) has been tested in PCR performed with cDNA derived from peripheral blood lymphocytes; it was shown not to alter the amplification of the V subfamily-specific DNA fragments. This panel of oligonucleotides will be helpful in the study of TcRV gene segment usage and, thus, may lead to a better characterization of T cell responses in physiological and pathological situations.

Base Sequence↗
PubMed2005

Impact of reservoir potentials on the analyte behavior in microchip electrophoresis: computer simulation and experimental validation for DNA fragments.

Fundamental understanding of the impact of reservoir potentials on the analyte behavior on the microfluidic chips is an important issue in microchip electrophoresis (MCE) for suitable injection and separation of analytes, since the applied potentials may significantly affect the shape of sample plug, sample leakage from the injection channel to the separation channel, injected sample amount, and separation efficiency. This study addressed this issue for the case of a conventional cross-geometry microchip with four reservoirs using computer simulations, the results of which were verified by the analysis of DNA fragments. For the microchip with a definite structure and migration distance, the injected sample amount was shown to be the vital parameter for improving the limit of detection and resolution. During injection, the shape of the sample plug could be adjusted by varying the reservoir potentials. It was demonstrated that a "magnified injection" (applying high voltage on the three reservoirs to the sample reservoir) is useful to enhance the detection sensitivity depending on the analyte composition, although such injection was previously avoided because of introducing too large amounts of the analyte in comparison with two established modes, floating and pinched injection. Optimal magnified injection was proved to improve the sensitivity for about 4 times over that of pinched injection for the analysis of DNA step ladders using microchip gel electrophoresis (MCGE). Sample leakage of DNA fragments could be suppressed by applying a high positive voltage on injection channel during separation, but the voltage degraded the injected amount and resolution.

Computer Simulation↗