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At least 145 records · Page 8Linked to original sources

Determination of 3D cartilage thickness data from MR imaging: computational method and reproducibility in the living.

The objective of this work was to develop a computational approach for quantifying the three-dimensional (3D) thickness distribution of articular cartilage with magnetic resonance (MR) imaging, independent of the imaging plane, and to test the reproducibility of the method in the living. An algorithm was implemented, based on a 3D Euclidean distance transformation, and its accuracy was assessed in geometric test objects, for which an analytic solution was available. The precision of the method was evaluated in six replicated MR data sets of the knee joint cartilage of eight volunteers. The algorithm produced 3D thickness values identical to those of the analytic solutions in the test objects. The reproducibility of the mean cartilage thickness in the patellar and tibial cartilages was 1.5-3.4% (root-mean-square average of the individual coefficient of variation percent), that of the maximal thickness 2.1-7.9%, and that of the thickness distribution 2.3-6.1%. The method presented allows for noninvasive analysis of 3D cartilage thickness from MR images in biomechanical and clinical investigations.

Algorithms↗

An improved computational method to assess pituitary responsiveness to secretagogue stimuli.

OBJECTIVE: The quantitative assessment of gland responsiveness to exogenous stimuli is typically carried out using the peak value of the hormone concentrations in plasma, the area under its curve (AUC), or through deconvolution analysis. However, none of these methods is satisfactory, due to either sensitivity to measurement errors or various sources of bias. The objective was to introduce and validate an easy-to-compute responsiveness index, robust in the face of measurement errors and interindividual variability of kinetics parameters. DESIGN: The new method has been tested on responsiveness tests for the six pituitary hormones (using GH-releasing hormone, thyrotrophin-releasing hormone, gonadotrophin-releasing hormone and corticotrophin-releasing hormone as secretagogues), for a total of 174 tests. Hormone concentrations were assayed in six to eight samples between -30 min and 120 min from the stimulus. METHODS: An easy-to-compute direct formula has been worked out to assess the 'stimulated AUC', that is the part of the AUC of the response curve depending on the stimulus, as opposed to pre- and post-stimulus spontaneous secretion. The weights of the formula have been reported for the six pituitary hormones and some popular sampling protocols. RESULTS AND CONCLUSIONS: The new index is less sensitive to measurement error than the peak value. Moreover, it provides results that cannot be obtained from a simple scaling of either the peak value or the standard AUC. Future studies are needed to show whether the reduced sensitivity to measurement error and the proportionality to the amount of released hormone render the stimulated AUC indeed a valid alternative to the peak value for the diagnosis of the different pathophysiological states, such as, for instance, GH deficits.

Adolescent↗

Simple computer method for evaluation of lateral diffusion coefficients from fluorescence photobleaching recovery kinetics.

A method is presented for the analysis of fluorescence photobleaching recovery curves. Based on the simplified kinetic expression of Yguerabide, J., J.A. Schmidt, and E.E. Yguerabide (1982, Biophys. J., 40:69-75), a linearization procedure is described that permits unequivocal determination of all diffusion parameters. The presence of additional membrane flow or multiple diffusion coefficients can easily be detected by this method, and simple corrections for the presence of these alternative recovery processes can be made by the use of a regular mini-computer. The validity of the method is tested on simulated recovery curves, varying the contribution of flow, multiple diffusion coefficients, and statistical noise due to counting error.

Diffusion↗

Computational methods for sequence mapping of large combinatorial libraries and deduced sequence signatures.

Here we describe a computational approach for the high-throughput sequence mapping of combinatorial libraries obtained by DNA shuffling. Original algorithms and their software implementation were developed for the automated and reliable analysis of hybridization data of differentially labeled oligonucleotide probes with PCR products spotted on DNA microarrays. This novel approach allows a context-dependent sequence attribution tolerant to fluctuations in experimental conditions and is well adapted to hybridization signals of variable qualities resulting from high-throughput PCR amplification from colonies. In addition, the analysis permits the calculation of sequence signatures that are characteristic of combinatorial library structure, defects, and diversity. The approach is of interest for the characterization and the equalization (library reduction to nonredundant structures) of combinatorial libraries involved in directed evolution and could be extrapolated to high-throughput polymorphism analysis.

Biotechnology↗

Manual versus computer methods for diagnosing obstruction from pressure-flow tracings in patients with benign prostatic hyperplasia.

PURPOSE: We compared manual versus computer analysis of pressure-flow tracings for diagnosing bladder outlet obstruction in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 105 patients with a clinical diagnosis of prostate enlargement and lower urinary tract symptoms was included in the study irrespective of free flow rates. Pressure-flow studies were performed in duplicate and tracings were evaluated by 2 independent investigators blinded to patients status. Manual reading of urodynamic printouts and fully computerized analysis using CLIM software were done. All urodynamic parameters relevant to the diagnosis of outlet obstruction were compared using the Abrams-Griffiths and Schäfer nomograms. Group specific urethral resistance factors were also compared. RESULTS: There was good correlation between manual and computer derived values of maximum flow (r = 0.9874, p < or = 0.0001), detrusor pressure at maximum flow (r = 0.9943, p < or = 0.0001), minimum detrusor pressure during voiding (r = 0.8816, p < or = 0.0001) and group specific urethral resistance factor (r = 0.9917, p < or = 0.0001). The diagnosis of outlet obstruction according to the group specific urethral resistance factor, and the Abrams-Griffiths and Schäfer nomograms was highly consistent using the manual and computerized approaches. CONCLUSIONS: Manual analysis of pressure-flow tracings generated by urodynamic equipment and digital data obtained by CLIM software appeared to be highly consistent and equally reliable for diagnosing and grading outlet obstruction.

Aged↗

Development of a multi-copy integration platform in Kluyveromyces marxianus enabled by a computational method for genome-wide identification of multi-copy integration loci.

Multi-copy integration is a core strategy for redirecting metabolic flux toward target compounds. However, its application has been hampered by the absence of methods for systematically identifying native multi-copy genomic loci. To overcome this, we developed a computational procedure for genome-wide identification of such loci. Theoretically, this method is potentially applicable to any genome-sequenced species as it only requires the genomic assembly of the target species as input. Applying the procedure to Kluyveromyces marxianus, we identified four groups of loci (KmCS1-4). Combining these loci-KmCS1-4 and the traditional 26S rDNA-with 14 markers with graded selection strengths, we established a versatile multi-copy integration toolkit comprising 70 plasmids. Each plasmid exhibits a unique integration pattern, collectively forming an integration profile. This profile serves as a manual, enabling users to select appropriate tools tailored to the expression requirements of rate-limiting enzymes in their pathways. Applying representative plasmids exhibiting low-, medium-, and high-copy integration patterns to lycopene biosynthesis modules resulted in lycopene titers of 3.5, 6.8 and 40.5&#x202f;mg/L, corresponding to 2, 6 and 9 genomic copies, respectively, demonstrating a positive correlation between lycopene titers, genomic copy numbers and integration patterns, which highlights the versatility of the toolkit and its supporting manual. Our study not only provides a broadly applicable methodology for genome-wide identification of multi-copy loci, but also an efficient integration platform for K. marxianus.

Kluyveromyces marxianus↗

[A computer method for assessing the average rate of movement of Paramecium caudatum by a cross-sectional light beam].

The possibility of using the motility of Paramecium caudatum for computer biotesting of toxic substances was studied. The method is based on measuring the number and duration of impulses that arise when protozoa chaotically moving in a layer 0.5 mm thick cross a red light beam (1 mm in diameter). It was found that, in the presence of Cu2+ ions and menadione bisulfite, a compound having prooxidant properties, the number of impulses decreased with a concurrent increase in the duration of impulses. The high correlation between the number of impulses and the reciprocal of impulse duration indicates that the motility of paramecium by the action of Cu2+ ions and menadione slow down, and even an immobilization of some of them occurs. The mean swimming velocity of protozoa was reduced by half within 20 min by the action of Cu2+ at a concentration of 90 microM (6 mg/l of Cu2+ ions) and within 80 min by the action of menadione bisulfite at a concentration of 50 microM. It was shown that the slowing down of motility, which indicates the presence of a toxicant in the medium, is a faster physiological reaction than cell death.

Animals↗

A versatile computational method for the determination of areas under the curve and moment curve following multidose drug administration.

The accurate determination of area under the biologic fluid concentration-time curve (AUC) and area under the first moment curve (AUMC) are important in the calculation of a compound's pharmacokinetic parameter estimates. Although numerous mathematical methods exist for the calculation of both AUC and AUMC under varying conditions, some permit direct computation of areas, whereas others only approximate the true areas. In this study, we describe an alternative mathematical method which allows the direct calculation of either the AUC or AUMC after any dose of drug administered by any route. Simulated data with known areas were used to assess the accuracy of the proposed method and compared to area calculations obtained from widely used published methods. Experiments were also performed under conditions of varying elimination half-lives and reduced numbers of concentration-time values. Under any experimental condition, the newly proposed method was the most accurate in determining both the AUC and AUMC. Percent deviations from exact area values were less than or equal to 0.11% with the proposed method, whereas as much as 30% deviation was observed using other methods of calculation. These findings support the accuracy of the proposed method in calculating the AUC or AUMC and its utility in data analysis.

Infusions, Intravenous↗