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Self-organising learning control and its application to muscle relaxant anaesthesia.

The concept of a self-organising control system is attractive in biomedicine because of the imprecise nature of available physiological models. In this paper a particular strategy called a self-organising controller (SOC) originating from the work of Barron on aerospace systems is applied to the control of muscle relaxant anaesthesia. The SOC algorithm, which requires no prior knowledge of system dynamics, is described, both in single variable and multivariable format. Simulation results are presented for SOC performance on a well-established pancuronium model. Three implementations are described, being the use of a general purpose language, a SUN workstation approach, and a parallel computer transputer solution. The latter approach becomes important for multivariable control because of the computing-intensive nature of SOC. The transputer is shown to be a suitable vehicle for implementation in terms of speed and parallelism for SOC.

Algorithms↗

Kinetic parameter estimation from compartment models using a genetic algorithm.

Kinetic parameters were estimated from a three-compartment fluorodeoxyglucose model with three rate constants using a genetic algorithm. The performance of the genetic algorithm was investigated by simulation studies, in which brain time-activity data (TAD) were generated using cited mean values of rate constants and the plasma TAD obtained from positron emission tomographic studies. The accuracy of kinetic parameter estimation using the genetic algorithm was compared with that using the non-linear least-squares (NLSQ) method. The margin of error in the parameters estimated using the genetic algorithm tended to be smaller than that obtained by the NLSQ method. Although not statistically significant at a noise level of 5% in the brain TAD, the difference between the two methods became significant for all parameters at a noise level of 15% or higher. Our results suggest that the genetic algorithm is a promising means of estimating kinetic parameters from compartment models, because it is more robust against statistical noise than the NLSQ method and it can be rendered highly parallel for processing.

Algorithms↗

Global and site-specific detection of human integrin alpha 5 beta 1 glycosylation using tandem mass spectrometry and the StrOligo algorithm.

Glycans are oligosaccharides associated with proteins, and are known to confer specific functions and conformations on glycoproteins. As protein tridimensional structures are related to function, the study of glycans and their impact on protein folding can provide important information to the field of proteomics. The subdiscipline of glycomics (or glycoproteomics) is rapidly growing in importance as glycans in proteins have shown to be involved in protein-protein or protein-(drug, virus, antibody) interactions. Glycomics studies most often aim at identifying glycosylation sites, and thus are performed on deglycosylated proteins resulting in loss of site-specific details concerning the glycosylation. In order to obtain such details by mass spectrometry (MS), either whole glycoproteins must be digested and analyzed as mixtures of peptides and glycopeptides, or glycans must be isolated from glycopeptide fractions and analyzed as pools. This article describes parallel experiments involving both approaches, designed to take advantage of the StrOligo algorithm functionalities with the aim of characterizing glycosylation microheterogeneity on a specific site. A hybrid quadrupole-quadrupole-time-of-flight (QqTOF) instrument equipped with a matrix-assisted laser desorption/ionization (MALDI) source was used. Glycosylation of alpha 5 beta 1 subunits of human integrin was studied to test the methodology. The sample was divided in two aliquots, and glycans from the first aliquot were released enzymatically, labelled with 2-aminobenzamide, and identified using tandem mass spectrometry (MS/MS) and the StrOligo program. The other aliquot was digested with trypsin and the resulting peptides separated by reversed-phase high-performance liquid chromatography (HPLC). A specific collected fraction was then analyzed by MS before and after glycan release. These spectra allowed, by comparison, detection of a glycopeptide (several glycoforms) and elucidation of peptide sequence. Compositions of glycans present were proposed, and identification of possible glycan structures was conducted using MS/MS and StrOligo.

Algorithms↗

New algorithm to model protein-protein recognition based on surface complementarity. Applications to antibody-antigen docking.

A novel algorithm is presented which models protein-protein interactions using surface complementarity. The method is applied to antibody-antigen docking. A steric scoring scheme, based upon a soft potential, is used to assess complementarity, and a simple electrostatic model is then used to remove infeasible interactions. The soft potential allows for structural changes that occur during docking. Biochemical knowledge is necessary to reduce the number of docking orientations produced by the method to a manageable size. The information used includes the known epitope residues and a single loose distance constraint. The method is applied to all three crystallographically determined antibody-lysozyme complexes, HyHEL-10, D1.3 and HyHEL-5. For the first time, a predicted antibody structure (that of D1.3) is used as a docking target. In the four systems modelled, the method identifies between 15 and 40 possible docking orientations. The root-mean-square (r.m.s.) deviation between these orientations and the relevant crystallographic complex is measured in the interface region. For all four complexes an orientation is found with r.m.s. deviation in the range 1.9 A and 4.8 A. The algorithm is implemented on a single instruction/multiple datastream (SI/MD) architecture computer. The use of a parallel architecture computer ensures detailed coverage of the search space, whilst still maintaining a search time of two days.

Algorithms↗

AxML: a fast program for sequential and parallel phylogenetic tree calculations based on the maximum likelihood method.

Heuristics for the NP-complete problem of calculating the optimal phylogenetic tree for a set of aligned rRNA sequences based on the maximum likelihood method are computationally expensive. In most existing algorithms the tree evaluation and branch length optimization functions, calculating the likelihood value for each tree topology examined in the search space, account for the greatest part of overall computation time. This paper introduces AxML, a program derived from fastDNAml, incorporating a fast topology evaluation function. The algorithmic optimizations introduced, represent a general approach for accelerating this function and are applicable to both sequential and parallel phylogeny programs, irrespective of their search space strategy. Therefore, their integration into three existing phylogeny programs rendered encouraging results. Experimental results on conventional processor architectures show a global run time improvement of 35% up to 47% for the various test sets and program versions we used.

Algorithms↗

Automated comet assay analysis.

BACKGROUND: Recently the "comet assay" or "single-cell gel electrophoresis assay" has been established as a sensitive method for the detection of DNA damage and repair. Most of the software now available to quantify various parameters for DNA damage requires the interaction of a human observer. In this report, we describe an automated analysis system that is based on self-developed software and hardware and needs minimal human interaction. METHODS: The image analysis is divided into two parts: 1) automatic cell recognition and comet classification and 2) quantification of desired comet parameters. Image preprocessing, segmentation, and feature classification were developed with algorithms based on mathematical morphology. To enhance evaluation speed, we have introduced parallel processing of data under the Windows NT operating system (Microsoft Corporation, Redmond, WA). Use of an analogue real-time autofocus unit (Böcker et al.: Phys Med Biol 1997;42:1981-1992) allows for faster analysis. RESULTS: Our recognition software shows a sensitivity of 95.2% and a specificity of 92.7% when tested on test samples from routine work with DNA damage by low-dose radiation (0-2 Gy). The parallel hardware and software concept enables us to analyze 100 comets on one slide in less than 15 min. CONCLUSIONS: A comparison of measurements made on the same samples by manual and automated analysis systems revealed that there are no significant differences. The slope of the dose-response curves and the repair kinetics are very similar and demonstrate that automatic comet assay analysis is possible.

Algorithms↗

Competitive interaction of the antitumor drug daunorubicin and the fluorescence probe ethidium bromide with DNA as studied by resolving trilinear fluorescence data: the use of PARAFAC and its modification.

The competitive interaction with DNA of daunorubicin (DR), being present in the clinical anti-tumor drug daunoblastina, and the fluorescence probe ethidium bromide (EB) has been studied by parallel-factor analysis (PARAFAC) and full-rank parallel-factor analysis (FRA-PARAFAC) of a fluorescence excitation-emission three-way data array. The PARAFAC algorithm can furnish stable resolution results for the data array studied, if the estimated number of chemical components is consistent with the real number. The FRA-PARAFAC algorithm is not sensitive to the estimated number of components of the fluorescence data array if the estimated number is not less than the real number. Both algorithms gave identical resolution for the three components concerned DR, EB, and the complex EB-DNA. Variations of the equilibrium concentrations of free DR, EB, and the complex EB-DNA were resolved by both algorithms. Experimental observation confirms the hypothesis that DR is an intercalator of DNA and that the binding interactions of DR and EB with DNA are a pair of parallel competitive intercalation reactions on same base sites of DNA. The method exemplified by this study provides a useful approach for studying competitive interactions of different drugs with DNA in the presence of interferents.

Algorithms↗

Efficient clustering of large EST data sets on parallel computers.

Clustering expressed sequence tags (ESTs) is a powerful strategy for gene identification, gene expression studies and identifying important genetic variations such as single nucleotide polymorphisms. To enable fast clustering of large-scale EST data, we developed PaCE (for Parallel Clustering of ESTs), a software program for EST clustering on parallel computers. In this paper, we report on the design and development of PaCE and its evaluation using Arabidopsis ESTs. The novel features of our approach include: (i) design of memory efficient algorithms to reduce the memory required to linear in the size of the input, (ii) a combination of algorithmic techniques to reduce the computational work without sacrificing the quality of clustering, and (iii) use of parallel processing to reduce run-time and facilitate clustering of larger data sets. Using a combination of these techniques, we report the clustering of 168 200 Arabidopsis ESTs in 15 min on an IBM xSeries cluster with 30 dual-processor nodes. We also clustered 327 632 rat ESTs in 47 min and 420 694 Triticum aestivum ESTs in 3 h and 15 min. We demonstrate the quality of our software using benchmark Arabidopsis EST data, and by comparing it with CAP3, a software widely used for EST assembly. Our software allows clustering of much larger EST data sets than is possible with current software. Because of its speed, it also facilitates multiple runs with different parameters, providing biologists a tool to better analyze EST sequence data. Using PaCE, we clustered EST data from 23 plant species and the results are available at the PlantGDB website.

Algorithms↗

A parallel approach to STAP implementation for fMRI data.

PURPOSE: To exploit the capabilities of parallel processing in applying the space-time adaptive processing (STAP) algorithm, previously explored on a small scale for functional magnetic resonance imaging (fMRI) applications, to conventional size fMRI data sets. MATERIALS AND METHODS: STAP is a two-dimensional filter that is able to locate fMRI activations in both space and frequency. It is applied here for the construction of brain activation maps in fMRI using Visual Age C, incorporating Engineering and Scientific Subroutine Library (ESSL) functions, compiled in 64-bit, and executed on an IBM SP supercomputer. RESULTS: Computer simulations incorporating actual MRI noise indicate that STAP, incorporated using the method of steepest descent, is feasible on conventional size data sets and exhibits an improvement in detecting activations over the more traditional cross correlation method of fMRI analysis when the response is unknown. CONCLUSION: STAP is feasible on traditional size fMRI data sets and useful in elucidating spatial and temporal connectivity.

Algorithms↗

Base-rate effects in category learning: a comparison of parallel network and memory storage-retrieval models.

Exemplar-memory and adaptive network models were compared in application to category learning data, with special attention to base rate effects on learning and transfer performance. Subjects classified symptom charts of hypothetical patients into disease categories, with informative feedback on learning trials and with the feedback either given or withheld on test trials that followed each fourth of the learning series. The network model proved notably accurate and uniformly superior to the exemplar model in accounting for the detailed course of learning; both the parallel, interactive aspect of the network model and its particular learning algorithm contribute to this superiority. During learning, subjects' performance reflected both category base rates and feature (symptom) probabilities in a nearly optimal manner, a result predicted by both models, though more accurately by the network model. However, under some test conditions, the data showed substantial base-rate neglect, in agreement with Gluck and Bower (1988b).

Adult↗

Data collection for cross-sectional image reconstruction by a moving ring of positron annihilation detectors.

A ring of positron annihilation detectors capable of two independent motions in the plane of the ring is considered. It can rotate around its center, and the whole ring may move so that its center traces a circular path. Provided certain parameters are chosen according to given formulas, data collected by such a detector ring can be reorganized (rebinned), in a computationally very inexpensive fashion, so that the data items in each bin are measurements along parallel lines spaced at small equal intervals. Efficient high resolution reconstruction algorithms that assume such data organization can therefore be applied to data collected collected by a moving positron ring detector. The method is demonstrated on a realistic example.

Computers↗

Heart rate variability characterization in daily physical activities using wavelet analysis and multilayer fuzzy activity clustering.

A portable data recorder was developed to parallel measure the electrocardiogram and body accelerations. A multilayer fuzzy clustering algorithm was proposed to classify the physical activity based on body accelerations. Discrete wavelet transform was incorporated to retrieve time-varying characteristics of heart rate variability under different physical activities. Nine healthy subjects were included to investigate activity-related heart rate variability during 24 h. The results showed that the heartbeat fluctuations in high frequencies were the greatest during lying and the smallest during standing. Moreover, very-low-frequency heartbeat fluctuations during low activity level (lying) were greater than during high activity level (nonlying).

Activities of Daily Living↗

A new method for computer-assisted determination of airways resistance.

Conventional methods for determining airways resistance, based on the recording of pressure and flow as X-Y displays, may yield inconsistent results because airways resistance is only one of a number of factors determining the shape of such displays. The temporal behavior of alveolar pressure and flow during panting suggests that the relationship between pressure and flow should be formulated in terms of differential equations. An equation is postulated to include terms characterizing resistance, gas inertance, and the behavior of the lungs as a number of parallel compartments with time constants that may be different. A simple algorithm allows these terms to be deduced from measured pressure and flow signals. Measurements obtained using the new method correlate well with those obtained using conventional methods. Variation of specific airways conductance is significantly reduced when compared with values obtained by conventional methods. Measured values for inertance agree well with theoretically predicted values.

Airway Resistance↗

Assessment of methacholine-induced airway constriction by ultrafast high-resolution computed tomography.

Assessment of changes in airway dimensions during bronchoconstriction is conventionally based on measurements of respiratory mechanics. We evaluated the efficacy of ultrafast high-resolution computed tomography (UHRCT) to directly determine the dynamic changes in cross-sectional area (CSA) of airways in response to methacholine (MCh). UHRCT scans were obtained at functional residual capacity before (baseline) and after intravenous bolus injections of MCh (10(-8.5)-10(-7.0) mol/kg) to seven mechanically ventilated pigs. Changes in CSA of bronchi of varying baseline size (1-10 mm diam) were determined by using a customized image processing software package (VIDA) based on a user-directed computer-adjusted edge-finding algorithm. MCh induced dose-dependent decreases in CSA, which were paralleled by increases in airway opening pressure at higher doses of MCh; at lower doses of MCh, decreases in CSA of smaller airways were detected without concomitant changes in airway opening pressure. Changes in CSA were heterogeneous and variable, especially in the smaller airway ranges. The results of the present study support the concept that UHRCT can be used in conjunction with bolus challenges to effectively determine dose-response changes in airway caliber in both large and small airways. This technique provides data that may not be reflected by conventional lung function measurements and, hence, is a useful tool to study airway reactivity.

Animals↗

Laboratory measurements of spectral reflection from ice clouds of various habits.

Spectral light from 550 to 650 nm reflected from the surface of an ice cloud produced in a temperature-controlled column is measured at seven different angles between 16.7 degrees and 29.9 degrees . Cloud optical depth (tau) is determined from the extinction of a 670 nm laser and is corrected for forward scattering using a Monte Carlo ray-tracing algorithm. Reflection measurements are compared to expectations from a plane-parallel radiative transfer model with input parameters based on the measured tau and a phase function for the observed ice crystal types. The plane-parallel radiative transfer model can be used to interpret the measured reflection for tau less than about 0.4 for this particular experiment, ideal for providing a validation data set to assist with the development of satellite bidirectional remote sensing.

Journal Article↗

[Cardiac magnetic resonance. Optimization of the parameters in the evaluation of right and left ventricular function].

MR imaging is the only non-invasive tomographic imaging modality capable of imaging the heart along planes that are parallel to each other and in any desired direction. Such reconstruction algorithms can thus be applied to MR images as the Simpson's rule which allows volume estimation of all cardiac cavities, although very irregular in shape, like the right ventricle. The authors optimized the technical parameters to obtain a set of multiphase double-angulated images on both the short and the long axes of the heart, in about 1-hour time. This technique was used to examine 31 patients suffering from several cardiopathies. The images allowed both end-diastolic and end-systolic volumes to be estimated, as well as the ejection fractions of both ventricles. In the left ventricle the area-length method and the Simpson's rule were applied, whereas only the latter was employed in the right ventricle. The correlation coefficients of US and MR data were, for the 3 parameters, r = 0.813, r = 0.920, and r = 0.879, respectively, in the first case, and r = 0.905, r = 0.923, and r = 0.890 in the second one. The time required to analyze the obtained data, which is done manually, is still considerably long.

Cardiac Volume↗

[Cyclic conformation of parallel polypeptide chains closed by cross bridges].

The method of possible conformations calculations for cyclic structures, formed by two (or more) identical parallel polypeptide chains, closed by cross bridges has been elaborated. The algorithm is necessary for rigorous conformational analysis of cyclic regions in immunoglobulin, fibronectin and myosin.

Models, Molecular↗

Ultra-high resolution SPECT system using four pinhole collimators for small animal studies.

UNLABELLED: We describe a newly developed ultra-high resolution SPECT system using four pinhole collimators for small animal studies. METHODS: The system utilizes a clinical four-head SPECT scanner with specially designed pinhole collimators. Four types of pinholes with different configurations were designed with different effective aperture sizes (1.0, 2.0 and 4.0 mm) and rotating radii (40 mm and 50 mm). The distance from the axis of rotation to the scintillator was fixed to 180 mm. A filtered backprojection algorithm was used to reconstruct SPECT images after fanbeam-to-parallel-beam data conversion. RESULTS: The system provided a reconstructed spatial resolution of 1.65 mm (FWHM) and sensitivity of 4.3 kcps/microCi/ml with the best type of pinholes, respectively. The 99mTc-HMPAO SPECT image in rat studies clearly visualized small brain structures, and the left ventricular myocardium and cardiac cavity were clearly separated with 99mTc-MIBI. Dynamic SPECT imaging of rat brain with [123I]iomazenil was also feasible. CONCLUSION: This ultra-high resolution SPECT system can be used to measure the regional distribution of radiolabeled tracers in small animals in vivo and may play a significant role in the development of new radiopharmaceuticals and in studies of various disease models using living animals.

Animals↗