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Iterative tomographic image reconstruction using Fourier-based forward and back-projectors.

Iterative image reconstruction algorithms play an increasingly important role in modern tomographic systems, especially in emission tomography. With the fast increase of the sizes of the tomographic data, reduction of the computation demands of the reconstruction algorithms is of great importance. Fourier-based forward and back-projection methods have the potential to considerably reduce the computation time in iterative reconstruction. Additional substantial speed-up of those approaches can be obtained utilizing powerful and cheap off-the-shelf fast Fourier transform (FFT) processing hardware. The Fourier reconstruction approaches are based on the relationship between the Fourier transform of the image and Fourier transformation of the parallel-ray projections. The critical two steps are the estimations of the samples of the projection transform, on the central section through the origin of Fourier space, from the samples of the transform of the image, and vice versa for back-projection. Interpolation errors are a limitation of Fourier-based reconstruction methods. We have applied min-max optimized Kaiser-Bessel interpolation within the nonuniform FFT (NUFFT) framework and devised ways of incorporation of resolution models into the Fourier-based iterative approaches. Numerical and computer simulation results show that the min-max NUFFT approach provides substantially lower approximation errors in tomographic forward and back-projection than conventional interpolation methods. Our studies have further confirmed that Fourier-based projectors using the NUFFT approach provide accurate approximations to their space-based counterparts but with about ten times faster computation, and that they are viable candidates for fast iterative image reconstruction.

Algorithms↗

Model-free reconstruction of three-dimensional myocardial strain from planar tagged MR images.

A technique is presented for reconstructing a three-dimensional myocardial strain map from a set of parallel-tagged MR images. Radial strains were reconstructed from in vivo data from an anesthetized dog with values between .05 and .1 with a precision of +/- .003 for a tag detection accuracy of .1 mm and a tag spacing of 2.5 mm. The reconstruction spatial resolution was demonstrated by reconstructing a localized displacement abnormality. In the circumferential direction, the abnormality that resulted in 50% displacement attenuation had a full width at half maximum of 5.4 +/- .4 mm (mean +/- SD). Graphs are presented showing the relationship between the size of an abnormality and the ability of the method to reconstruct that abnormality. The combination of high resolution parallel-tagged MR images and the model-free, coordinate system-free strain reconstruction technique presented in this paper is capable of producing accurate, high resolution strain maps of the myocardium.

Algorithms↗

Computer vision based analysis of potato chips--a tool for rapid detection of acrylamide level.

In this study, analysis of digital color images of fried potato chips were combined with parallel LC-MS based analysis of acrylamide in order to develop a rapid tool for the estimation of acrylamide during processing. Pixels of the fried potato image were classified into three sets based on their Euclidian distances to the representative mean values of typical bright yellow, yellowish brown, and dark brown regions using a semiautomatic segmentation algorithm. The featuring parameter extracted from the segmented image was NA2 value which was defined as the number of pixels in Set-2 divided by the total number of pixels of the entire fried potato image. Using training images of potato chips, it was shown that there was a strong linear correlation (r = 0.989) between acrylamide level and NA2 value. Images of a number of test samples were analyzed to predict their acrylamide level by means of this correlation data. The results confirmed that computer vision system described here provided explicit and meaningful description from the viewpoint of inspection and evaluation purpose for potato chips. Assuming a provisional threshold limit of 1000 ng/g for acrylamide, test samples could be successfully inspected with only one failure out of 60 potato chips.

Acrylamide↗

Beta-breakers: an aperiodic secondary structure.

We have studied the architecture of parallel beta-sheets in proteins and focused on the residues that initiate and terminate the beta-strands. These beta-breaker residues are at the origin of the kink between the beta-strand and the turn that precedes or follows it. beta-Breakers can be located automatically using a consensus approach based on algorithmic secondary structure assignment, solvent accessibility and backbone dihedral angles. These beta-breakers are conformationally homogeneous with respect to side-chain solvent accessibility and backbone dihedral angle profile. A sequence-structure correlation is noted: a restricted subset of amino acids is observed at these positions. Analysis of homologous protein sequences shows that these residues are more highly conserved than other residues in the loop. We conclude that beta-breakers are the structural analogs of the N and C-terminal caps of alpha-helices. The identification of this aperiodic substructure suggests a strategy for improving secondary structure prediction and may guide site-directed mutagenesis experiments.

Amino Acid Sequence↗

A high-throughput method to measure the sensitivity of yeast cells to genotoxic agents in liquid cultures.

The sensitivity of yeast Saccharomyces cerevisiae to DNA damaging agents is better represented when cells are grown in liquid media than on solid plates. However, systematic assessment of several strains that are grown in different conditions is a cumbersome undertaking. We report an assay to determine cell growth based on automatic measurements of optical densities of very small (100 microl) liquid cell cultures. Furthermore, an algorithm was elaborated to analyze large data files obtained from the cell growth curves, which are described by the growth rate--that starts at zero and accelerates to the maximal rate (mu(m))--and by the lag time (lambda). Cell dilution spot test for colony formation on solid media and the growth curve assay were used in parallel to analyze the phenotypes of cells after treatments with three different classes of DNA damaging agents (methyl methanesulfonate, bleomycin, and ultraviolet light). In these experiments the survival of the WT (wild type) and a number of DNA repair-deficient strains were compared. The results show that only the cell growth curve assay could uncover subtle phenotypes when WT cells, or mutant strains that are only weakly affected in DNA repair proficiency, were treated with low doses of cytotoxic compounds. The growth curve assay was also applied to establish whether histone acetyltransferases and deacetylases affect the resistance of yeast cells to UV irradiation. Out of 20 strains tested the sir2delta and rpd3delta cells were found to be more resistant than the WT, while gcn5delta and spt10delta cells were found to be more sensitive. This new protocol is sensitive, provides quantifiable data, offers increased screening capability and speed compared to the colony formation test.

Bleomycin↗

Computer simulation study of synthetic 4-helix bundle that binds halothane.

1. The synthetic peptide H10A24 self-assembles in aqueous solution into a 4-helix bundle, which exhibits saturable binding of halothane. 2. Molecular dynamics simulation techniques have been used to study the vacuum structure of this bundle. 3. The simulation, initiated as four ideal parallel alpha-helices, resulted in a compact bundle, whose secondary structure remains predominantly alpha-helical. 4. The hydrophobic core has no apparent pocket large enough to accomodate halothane.

Algorithms↗

RNA enzymes with two small-molecule substrates.

BACKGROUND: The 'RNA world' hypothesis posits ancient organisms employing versatile catalysis by RNAs. In particular, such a metabolism would have required RNA catalysts that join small molecules. Such anabolic reactions now occur very widely, for example in phospholipid, terpene, amino acid and nucleotide synthetic pathways in modern organisms. Present RNA systems, however, do not perform such reactions using substrates that do not base pair. Here we ask whether this lack is a methodological artifact due to the practice of selection-amplification, or a fundamental property of active sites reconstructed within RNA structures. RESULTS: Three rationally modified RNA enzymes, Iso6-G, Iso6-2G and Iso63G, catalyze the formation of (5'-->5') polyphosphate-linked oligonucleotides in trans. One of these, Iso6-G RNA, has a specific substrate site for a guanosine triphosphate, GTP, dGTP or ddGTP, and one nonspecific substrate site for a terminal-phosphate-containing small molecule. This ribozyme catalyzes multiple turnovers, proceeding at a constant rate. Guanosine specificity is probably not attributable to Watson-Crick base pairing. CONCLUSIONS: Ribozymes can readily bind multiple small-molecule substrates simultaneously and catalyze reactions that build up larger products, apparently independent of substrate-RNA Watson-Crick base pairing. RNA enzymes therefore parallel proteins, which often overcome the entropic difficulties of positioning multiple small substrates for catalysis of anabolic reactions. These results support the idea of a complex ancestral metabolism based on RNA catalysis.

Algorithms↗

Arabidopsis transcript profiling on Affymetrix GeneChip arrays.

DNA microarrays are becoming a frequently used research tool. Whilst several studies have confirmed the reproducibility of analysing the same RNA samples on duplicate arrays, there is little analysis of the reproducibility of the results of transcript profiling between microarrays carrying different probes to a common set of genes. To address this question, we compared the performance and reproducibility of two microarrays commonly used in plant research, the Affymetrix Arabidopsis AG array containing more than 8000 probe sets and the Affymetrix Arabidopsis ATH1 array containing more than 22,000 redesigned probe sets. A total of 21 different RNA samples were labelled and hybridized in parallel to the two microarray types. Focusing on the overlap of more than 7300 targets detected with both arrays, we found a high degree of reproducibility. Despite the use of different probe sets, both signal and signal log ratio were very similar for most genes. However, genes that were called absent or not changed by Affymetrix' statistical algorithm implemented in MAS5.0 showed considerably less conservation of expression patterns. Moreover, we identified about 300 genes that yielded strongly different measurements with the two microarrays, emphasizing that RNA profiling data need careful interpretation. Overall, this study shows that results obtained with ATH1 and AG arrays are very comparable and hence that the analysis is largely independent of probe sets. However, the result emphasize the need for appropriate filtering schemes such as those based on the present and change calls provided by MAS5.0 rather than reliance solely on signal values.

Arabidopsis↗

Increased metabolism of infused 1-methylxanthine by working muscle.

Exogenous substrates for capillary endothelial enzymes have potential as markers for changes in capillary recruitment (albeit nutritive flow). The metabolism of infused 1-methylxanthine (1-MX) to 1-methylurate (1-MU) by capillary endothelial xanthine oxidase of the constant-flow perfused rat hindlimb was shown previously to decrease with oxygen uptake (VO2) when nutritive flow was decreased. In the present study, the metabolism of 1-MX was investigated under conditions when VO2 and nutritive flow are known to increase during muscle contraction. The constant-flow red blood cell-perfused rat hindlimb at 37 degrees C was used with sciatic nerve stimulation, and perfusate samples from whole hindlimb and working muscles taken for analysis of oxygen, lactate, 1-MX and 1-MU. Flow to muscle was assessed separately using fluorescent microspheres and was found to increase 2.3-fold to the working muscles while flow to the non-working leg muscles decreased to compensate. The activity of xanthine oxidase of whole muscle extracts was not altered by contraction. Samples from the vein draining the working muscles, and microsphere measurements of flow, indicated increased VO2 (5.5-fold to 249.2 +/- 43.1 micromol h-1 g-1, P < 0.001), and 1-MX conversion (2.5-fold to 1.87 +/- 0.25 micromol h-1 g-1, P < 0.01) (SEM are shown). It is concluded that as 1-MX metabolism parallels VO2, this substrate may be a useful indicator of changes in capillary (nutritive) surface area in muscle.

Algorithms↗

Parallelized multiple alignment.

UNLABELLED: Multiple sequence alignment is a frequently used technique for analyzing sequence relationships. Compilation of large alignments is computationally expensive, but processing time can be considerably reduced when the computational load is distributed over many processors. Parallel processing functionality in the form of single-instruction multiple-data (SIMD) technology was implemented into the multiple alignment program Praline by using 'message passing interface' (MPI) routines. Over the alignments tested here, the parallelized program performed up to ten times faster on 25 processors compared to the single processor version. AVAILABILITY: Example program code for parallelizing pairwise alignment loops is available from http://mathbio.nimr.mrc.ac.uk/~jkleinj/tools/mpicode. The 'message passing interface' package (MPICH) is available from http:/www.unix.mcs.anl.gov/mpi/mpich. CONTACT: jhering@nimr.mrc.ac.uk SUPPLEMENTARY INFORMATION: Praline is accessible at http://mathbio.nimr.mrc.ac.uk/praline.

Algorithms↗

DPRml: distributed phylogeny reconstruction by maximum likelihood.

MOTIVATION: In recent years there has been increased interest in producing large and accurate phylogenetic trees using statistical approaches. However for a large number of taxa, it is not feasible to construct large and accurate trees using only a single processor. A number of specialized parallel programs have been produced in an attempt to address the huge computational requirements of maximum likelihood. We express a number of concerns about the current set of parallel phylogenetic programs which are currently severely limiting the widespread availability and use of parallel computing in maximum likelihood-based phylogenetic analysis. RESULTS: We have identified the suitability of phylogenetic analysis to large-scale heterogeneous distributed computing. We have completed a distributed and fully cross-platform phylogenetic tree building program called distributed phylogeny reconstruction by maximum likelihood. It uses an already proven maximum likelihood-based tree building algorithm and a popular phylogenetic analysis library for all its likelihood calculations. It offers one of the most extensive sets of DNA substitution models currently available. We are the first, to our knowledge, to report the completion of a distributed phylogenetic tree building program that can achieve near-linear speedup while only using the idle clock cycles of machines. For those in an academic or corporate environment with hundreds of idle desktop machines, we have shown how distributed computing can deliver a 'free' ML supercomputer.

Algorithms↗

Datamonkey: rapid detection of selective pressure on individual sites of codon alignments.

UNLABELLED: Datamonkey is a web interface to a suite of cutting edge maximum likelihood-based tools for identification of sites subject to positive or negative selection. The methods range from very fast data exploration to the some of the most complex models available in public domain software, and are implemented to run in parallel on a cluster of computers. AVAILABILITY: http://www.datamonkey.org. In the future, we plan to expand the collection of available analytic tools, and provide a package for installation on other systems.

Algorithms↗

The use of photogrammetry in tissue compensator design. Part II: experimental verification of compensator design.

A computer algorithm for designing sheet lead tissue compensators is described. Corrections are made for scatter within the radiation field as well as the shape of the patient for the mantle fields used in treating Hodgkin's disease. The method was tested experimentally with a phantom and found to be clinically acceptable. The advantages of employing this technique with parallel opposed fields are emphasized.

Hodgkin Disease↗

Parallel demodulation system and signal-processing method for extrinsic Fabry-Perot interferometer and fiber Bragg grating sensors.

A parallel demodulation system for extrinsic Fabry-Perot interferometer (EFPI) and fiber Bragg grating (FBG) sensors is presented that is based on a Michelson interferometer and combines the methods of low-coherence interference and Fourier transform spectrum. Signals from EFPI and FBG sensors are obtained simultaneously by scanning one arm of a Michelson interferometer, and an algorithm model is established to process the signals and retrieve both the wavelength of the FBG and the cavity length of the EFPI at the same time, which are then used to determine the strain and temperature.

Journal Article↗

High-accuracy DNA sequence variation screening by DHPLC.

Genetic maps based on biallelic single-nucleotide polymorphisms amenable to microarray-based genotyping have significantly accelerated the mapping of mono- and multigenic traits in model organisms such as Saccharomyces cerevisiae and Arabidopsis thaliana. This advance needs to be matched by highly accurate, inexpensive and robust methodology for fine-structure mapping of the candidate region(s) and the eventual identification of the causative mutation(s). To establish the usefulness of denaturing high-performance liquid chromatography (DHPLC) for those purposes, we have amplified 476 fragments from two A. thaliana ecotypes with an average length of 563 bp covering various candidate regions on chromosomes 1, 2 and 4. Parallel analysis by DHPLC and dye terminator sequencing showed that DHPLC detected 165 out of 166 polymorphic fragments with only four false positives, amounting to a sensitivity, specificity and accuracy of 99.4%, 98.7% and 99%, respectively. It proved beneficial to analyze the fragments not only at the highest but also at the lower temperatures recommended by the algorithm freely available at http:¿insertion.stanford.edu/melt.html.

Algorithms↗

Quantitative imaging of the structure and function of the heart, lungs, and circulation.

A 28-x-ray-source, cylindrical-scanning, transaxial tomographic x-ray-imaging system is in the process of being fabricated. This system will scan synchronously up to 250 parallel transverse cross sections of the human body over an axial range of 25 cm within 0.01 second at a maximum rate of 60 scans per second. The system will provide numerous variations of scanning configurations to permit quantitative assessment of the relative importance of transverse section thickness, image contrast, spatial and temporal resolution, and related computerized algorithms and display techniques. Synchronous imaging at high temporal resolution of a three-dimensional volume--for example, the heart--eliminates the need for successive periods of breath-holding and gated imaging techniques and is essential for quantitation of cardiovascular and pulmonary function and structure in intact animals or humans. Initial clinical applications are expected to be in the early detection of lung cancer and the diagnosis of the nature and degree of congenital and acquired cardiovascular disabilities.

Animals↗

The distributed representation of vestibulo-oculomotor signals by brain-stem neurons.

The vestibuloocular reflex and other oculomotor functions are subserved by populations of neurons operating in parallel. This distributed aspect of the system's organization has been largely ignored in previous block diagram models. Neurons that transmit oculomotor signals, such as those in the vestibular nucleus (VN), actually combine the different types of signals in a diverse, seemingly random way that could not be predicted from a block diagram. We used the backpropagation learning algorithm to program distributed neural-network models of the vestibulo-oculomotor system. Networks were trained to combine vestibular, pursuit and saccadic eye velocity command signals. The model neurons in these neural networks have diverse combinations of vestibulo-oculomotor signals that are qualitatively similar to those reported for actual VN neurons in the monkey. This similarity implicates a learning mechanism as an organizing influence on the vestibulo-oculomotor system and demonstrates how VN neurons can encode vestibulo-oculomotor signals in a diverse, distributed manner.

Algorithms↗

Simultaneous gene clustering and subset selection for sample classification via MDL.

MOTIVATION: The microarray technology allows for the simultaneous monitoring of thousands of genes for each sample. The high-dimensional gene expression data can be used to study similarities of gene expression profiles across different samples to form a gene clustering. The clusters may be indicative of genetic pathways. Parallel to gene clustering is the important application of sample classification based on all or selected gene expressions. The gene clustering and sample classification are often undertaken separately, or in a directional manner (one as an aid for the other). However, such separation of these two tasks may occlude informative structure in the data. Here we present an algorithm for the simultaneous clustering of genes and subset selection of gene clusters for sample classification. We develop a new model selection criterion based on Rissanen's MDL (minimum description length) principle. For the first time, an MDL code length is given for both explanatory variables (genes) and response variables (sample class labels). The final output of the proposed algorithm is a sparse and interpretable classification rule based on cluster centroids or the closest genes to the centroids. RESULTS: Our algorithm for simultaneous gene clustering and subset selection for classification is applied to three publicly available data sets. For all three data sets, we obtain sparse and interpretable classification models based on centroids of clusters. At the same time, these models give competitive test error rates as the best reported methods. Compared with classification models based on single gene selections, our rules are stable in the sense that the number of clusters has a small variability and the centroids of the clusters are well correlated (or consistent) across different cross validation samples. We also discuss models where the centroids of clusters are replaced with the genes closest to the centroids. These models show comparable test error rates to models based on single gene selection, but are more sparse as well as more stable. Moreover, we comment on how the inclusion of a classification criterion affects the gene clustering, bringing out class informative structure in the data. AVAILABILITY: The methods presented in this paper have been implemented in the R language. The source code is available from the first author.

Algorithms↗