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Implementation of spectral width Doppler in pulsatile flow measurements.

In this paper, we present an automatic beam-vector (Doppler) angle and flow velocity measurement method and implement it in pulsatile flow measurements using a clinical Doppler ultrasound system. In current clinical Doppler ultrasound flow velocity measurements, the axis of the blood vessel needs to be set manually on the B-scan image to enable the estimation of the beam-vector angle and the beam-vector angle corrected flow velocity (the actual flow velocity). In this study, an annular array transducer was used to generate a conical-shaped and symmetrically focused ultrasound beam to measure the flow velocity vectors parallel and perpendicular to the ultrasound beam axis. The beam-vector angle and flow velocity is calculated from the mode frequency (f(d)) and the maximum Doppler frequency (f(max)) of the Doppler spectrum. We develop a spectrum normalization algorithm to enable the Doppler spectrum averaging using the spectra obtained within a single cardiac cycle. The Doppler spectrum averaging process reduces the noise level in the Doppler spectrum and also enables the calculation of the beam-vector angle and flow velocity for pulsatile flows to be measured. We have verified the measurement method in vivo over a wide range of angles, from 52 degrees to 80 degrees, and the standard deviations of the measured beam-vector angles and flow velocities in the carotid artery are lower than 2.2 degrees and 12 cm/s (about 13.3%), respectively.

Blood Flow Velocity↗

Deep insight from simple models of evolution.

On one hand, people admire the often strikingly efficient results of organic evolution. On the other hand, however, they decry mutation and selection to be a rather prodigal, inefficient trial-and-error strategy. Taking into account the parallel information processing in a heterogeneous population and sexual propagation with recombination, as well as the genetic control of the reproduction accuracy, computer simulated evolution reveals a couple of interesting, sometimes surprising, properties of nature's learning-by-doing algorithm. Survival of the fittest, Spencer's résumé of Darwin's view, turns out to be a bad advice if taken literally. Individual death, forgetting, and even regression show up to be necessary ingredients of the life game. Whether the process should be named gradualistic or punctualistic, is a matter of the observer's point of view.

Algorithms↗

Functional MRI experiments: acquisition, analysis and interpretation of data.

Functional MRI is widely used to address basic and clinical neuroscience questions. In the key domains of fMRI experiments, i.e. acquisition, processing and analysis, and interpretation of data, developments are ongoing. The main issues are sensitivity for changes in fMRI signal that are associated with brain function, and the design of tasks with which brain functions are invoked. In this paper we address these issues, in terms of strengths, weaknesses and future developments. Acquisition of data is commonly achieved with techniques that measure blood oxygen level-dependent (BOLD) signal changes. Although the mechanisms that affect BOLD signal are complex and not well understood, fMRI yields results that agree with known functional topography. Sensitivity for task-related brain activity is expected to benefit from technological advances in acquisition, i.e. SENSE or parallel imaging, and higher field scanners (3 T). Data analysis is geared towards modelling sources of signal variation, i.e. reducing noise in the data time-series, and the cerebrovascular response to task-related changes in neuronal activity. Analytical algorithms such as connectivity and component analysis contribute to the extraction of meaningful information from fMRI datasets. The choice of tasks, and consequently of the statistical evaluation procedures, is best guided by the specific questions that are formulated a priori. The future is expected to bring more sophisticated questions, and tasks that allow for accurate modelling of involved brain functions. An example of a hypothesis-driven experiment is presented, where we investigated whether practise of a working memory task caused a shift in the neuronal representation of working memory or not.

Brain↗

Rapid analysis of hematology image data: the ADC-500 preprocessor.

A sequential, pipeline processor (that we have named the ADC-500 preprocessor) has been developed which scene segments the three color image data from the ADC-500 optics one image element at a time, groups together image elements from each object in the scene and extracts features from each object. The processing occurs at television frame rates, requiring 16.7 msec to process the entire image. This speed was instrumental in allowing the ADC-500 automated differential analyzer to perform routine 500-cell differentials. The preprocessor also contains hardware which simplifies compilation of the three color histograms. The segmentation algorithms implemented in the preprocessor are multicolor extensions of the classical monochrome density histogram threshold method. For most cell image analysis tasks, a sequential pipeline processor of this type should be more economical and as fast or faster than a parallel processor.

Blood Cells↗

A two-dimensional mathematical model of non-linear dual-sorption of percutaneous drug absorption.

BACKGROUND: Certain drugs, for example scopolamine and timolol, show non-linear kinetic behavior during permeation process. This non-linear kinetic behavior is due to two mechanisms; the first mechanism being a simple dissolution producing mobile and freely diffusible molecules and the second being an adsorption process producing non-mobile molecules that do not participate in the diffusion process. When such a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, C, the donor concentration. The present paper studies the effect of the parameter value, C, when the region of the contact of the skin with drug, is a line segment on the skin surface. To confirm that dual-sorption process gives an explanation to non-linear kinetic behavior, the characteristic features that are used in one-dimensional models are (1) prolongation of half-life if the plot of flux versus time are straight lines soon after the vehicle removal, (2) the decrease in half-life with increase in donor concentration. This paper introduces another feature as a characteristic to confirm that dual-sorption model gives an explanation to the non-linear kinetic behavior of the drug. This new feature is "the prolongation of half-life is not a necessary feature if the plots of drug flux versus time is a non-linear curve, soon after the vehicle removal". METHODS: From biological point of view, a drug absorption model is said to be nonlinear if the sorption isotherm is non-linear. When a model is non-linear the relationship between lag-time and donor concentration is non-linear and the lag time decreases with increase in donor concentration. A two-dimensional dual-sorption model is developed for percutaneous absorption of a drug, which shows non-linear kinetic behavior in the permeation process. This model may be used when the diffusion of the drug in the direction parallel to the skin surface must be examined, as well as in the direction into the skin, examined in one-dimensional models. The dual-sorption model is an initial/boundary value problem which consists of (1) one non-linear, two-dimensional, second-order parabolic equation, (2) boundary conditions, (3) one initial condition. Note that, the number of boundary conditions are, six and four, respectively, if the permeation process under consideration is, during the application of the vehicle and during the removal of the vehicle. Adopting the approach of method of lines, the initial/boundary value problem is transformed into an initial-value problem, which consists of (1) a system of non-linear ordinary differential equations, (2) one initial condition. The system of non-linear ordinary differential equations contains time-dependent non-homogeneous terms, if the permeation process under consideration is, during the application of the vehicle. To solve this initial-value problem, an eight-stage sequential algorithm which is second-order accurate, and requires only tri-diagonal solvers, is developed. RESULTS: Simulation of the numerical methods described is carried out with various values of the parameter C. The illustrations are given in the form of figures. The concentration profiles are viewed as parabolas along the mesh lines parallel to x-axis or y-axis. The flow rates in different subregions of the skin-region are studied. The shapes of the concentration profiles are examined before and after the steady-state concentration is reached. The concentration reaches steady-state when the flux reaches the steady state. The plots of flux versus time and cumulative amount of drug eliminated into the receptor cell versus time are given. CONCLUSION: Based on the various values of the parameter, C, conclusions are drawn about (1) flow rate of the drug in different regions of the skin, (2) shape of the concentration profiles, (3) the time required to reach the steady-state value of the concentration, (4) concentration of the drug in different regions of the skin, when steady-state value of the concentration is reached, (5) the time required to reach the steady-state value of the flux, (6) time required to reach the steady-state value of the concentration of the drug, (7) half-life of the concentration of the drug and (8) lag-time. A comparison, between this two-dimensional model and the one-dimensional non-linear dual-sorption model that exists in the literature, is done based on (1) the shape of the concentration profiles at various time levels, (2) the time required to reach the steady-state value of the concentration, (3) lag-time and (4) half-life.

Administration, Topical↗

An algorithm for the determination and quantification of components of nucleic acid mixtures based on single sequencing reactions.

BACKGROUND: Determination and quantification of nucleic acid components in a mixture is usually accomplished by microarray approaches, where the mixtures are hybridized against specific probes. As an alternative, we propose here that a single sequencing reaction from a mixture of nucleic acids holds enough information to potentially distinguish the different components, provided it is known which components can occur in the mixture. RESULTS: We describe an algorithm that is based on a set of linear equations which can be solved when the sequencing profiles of the individual components are known and when the number of sequenced nucleotides is larger than the number of components in the mixture. We have implemented the procedure for one type of sequencing approach, pyrosequencing, which produces a stepwise output of peaks that is particularly suitable for the procedure. As an example we use signature sequences from ribosomal RNA to distinguish and quantify several different species in a mixture. Using simulations, we show that the procedure may also be applicable for dideoxy sequencing on capillary sequencers, requiring only some instrument specific adaptations of protocols and software. CONCLUSION: The parallel sequencing approach described here may become a simple and cheap alternative to microarray experiments which aim at routine re-determination and quantification of known nucleic acid components from environmental samples or tissue samples.

Algorithms↗

Hidden Markov models and iterative aligners: study of their equivalence and possibilities.

There are many shared attributes between existing iterative aligners and Hidden Markov Model (HMM). A learning algorithm of HMM called Viterbi is the same as the iteration of DP-matching of iterative aligners. HMM aligners can use the result of an iterative aligner initially, incorporate the similarity score of amino acids, and apply the detailed gap cost systems to improve the matching accuracy. On the other hand, the iterative aligner can inherit the modeling capability of HMM, and provide the better representation of the proteins than motifs. In this paper, we present an overview of several iterative aligners which include the parallel iterative aligner of ICOT and the HMM aligner of Haussler's group. We compare the merits and shortcomings of these aligners. This comparison enables us to formulate a better, more advanced aligner through proper integration of the iterative technique and HMM technique.

Algorithms↗

The parallelization of SPIDER on distributed-memory computers using MPI.

We describe the strategies and implementation details we employed to parallelize the SPIDER software package on distributed-memory parallel computers using the message passing interface (MPI). The MPI-enabled SPIDER preserves the interactive command line and batch interface used in the sequential version of SPIDER, thus does not require users to modify their existing batch programs. We show the excellent performance of the MPI-enabled SPIDER when it is used to perform multi-reference alignment and 3-D reconstruction operations on a number of different computing platforms. We point out some performance issues when the MPI-enabled SPIDER is used for a complete 3-D projection matching refinement run, and propose several ways to further improve the parallel performance of SPIDER on distributed-memory machines.

Algorithms↗

Analysis of 3D transient blood flow passing through an artificial aortic valve by Lattice-Boltzmann methods.

The development of flow instabilities due to high Reynolds number flow in artificial heart valve geometries inducing high strain rates and stresses often leads to hemolysis and related highly undesired effects. Geometric and functional optimization of artificial heart valves is therefore mandatory. In addition to experimental work in this field it is meanwhile possible to obtain increasing insight into flow dynamics by computer simulation of refined model problems. After giving an introductory overview we report the results of the simulation of three-dimensional transient physiological flows in fixed geometries similar to a CarboMedics bileaflet heart valve at different opening angles. The visualization of emerging complicated flow patterns gives detailed information about the transient history of the systems dynamical stability. Stress analysis indicates temporal shear stress peaks even far away from walls. The mathematical approach used is the Lattice Boltzmann method. We obtained reasonable results for velocity and shear stress fields. The code is implemented on parallel hardware in order to decrease computation time. Finally, we discuss problems, shortcomings and possible extensions of our approach.

Algorithms↗

Folding probabilities: a novel approach to folding transitions and the two-dimensional Ising-model.

The theoretical concept of folding probability, p(fold), has proven to be a useful means to characterize the kinetics of protein folding. Here, we illustrate the practical importance of p(fold) and demonstrate how it can be determined theoretically. We derive a general analytical expression for p(fold) and show how it can be estimated from simulations for systems where the transition rates between the relevant microstates are not known. By analyzing the Ising model we are able to determine the scaling behavior of the numerical error in the p(fold) estimate as function of the number of analyzed Monte Carlo runs. We apply our method to a simple, newly developed protein folding model for the formation of alpha helices. It is demonstrated that our technique highly parallelizes the calculation of p(fold) and that it is orders of magnitude more efficient than conventional approaches.

Algorithms↗

Synchronization of trajectories in canonical molecular-dynamics simulations: observation, explanation, and exploitation.

For two methods commonly used to achieve canonical-ensemble sampling in a molecular-dynamics simulation, the Langevin thermostat and the Andersen [H. C. Andersen, J. Chem. Phys. 72, 2384 (1980)] thermostat, we observe, as have others, synchronization of initially independent trajectories in the same potential basin when the same random number sequence is employed. For the first time, we derive the time dependence of this synchronization for a harmonic well and show that the rate of synchronization is proportional to the thermostat coupling strength at weak coupling and inversely proportional at strong coupling with a peak in between. Explanations for the synchronization and the coupling dependence are given for both thermostats. Observation of the effect for a realistic 97-atom system indicates that this phenomenon is quite general. We discuss some of the implications of this effect and propose that it can be exploited to develop new simulation techniques. We give three examples: efficient thermalization (a concept which was also noted by Fahy and Hamann [S. Fahy and D. R. Hamann, Phys. Rev. Lett. 69, 761 (1992)]), time-parallelization of a trajectory in an infrequent-event system, and detecting transitions in an infrequent-event system.

Algorithms↗

A note on sample size calculation for mean comparisons based on noncentral t-statistics.

One-sample and two-sample t-tests are commonly used in analyzing data from clinical trials in comparing mean responses from two drug products. During the planning stage of a clinical study, a crucial step is the sample size calculation, i.e., the determination of the number of subjects (patients) needed to achieve a desired power (e.g., 80%) for detecting a clinically meaningful difference in the mean drug responses. Based on noncentral t-distributions, we derive some sample size calculation formulas for testing equality, testing therapeutic noninferiority/superiority, and testing therapeutic equivalence, under the popular one-sample design, two-sample parallel design, and two-sample crossover design. Useful tables are constructed and some examples are given for illustration.

Algorithms↗

Reduction of computational complexity in the butterfly search technique.

In the butterfly search technique, echoes from repeated firings of a transducer are resampled along a set of predetermined trajectories of constant velocities, called "butterfly lines," because of their intersection and crossing at a reference range. The slope of the trajectory on which the sampled signals satisfy a predetermined criterion appropriate for the type of signal in question, provides an estimate of the velocity of the target. The search for this trajectory is called "butterfly search," which can be carried out efficiently in a parallel processing scheme. The estimator can be based on the radio frequency (RF) A-lines, the envelopes, or the quadrature components. The butterfly search on quadrature components has shown outstanding noise immunity, even with relatively few successive scan lines, and was found to outperform all the common time domain and Doppler techniques in simulations and experiments with strong noise. It can be simply implemented using elementary digital signal processing hardware. However, it is possible to further improve upon its computational complexity to make the technique even simpler to implement, without any complex multipliers in the parallel channels. In this paper, we present some modifications that significantly reduce the computational complexity of butterfly search on quadrature components.

Algorithms↗

The transtheoretical model applied to an oral self-care behavioral change: development and testing of instruments for stages of change and decisional balance.

PURPOSE: The Transtheoretical Model is a theory-based approach for conceptualizing behavioral change. Inherent in this model is the determination and use of appropriate interventions to assist clients in improving their health behaviors. In the Transtheoretical Model, behavioral change progresses through a series of stages (precontemplation, contemplation, preparation, action, and maintenance) where movement from stage to stage is dependent upon decisional balance (the pros and cons that influence the decision). The purpose of this study was to develop instruments to test the validity and reliability of two components of the Transtheoretical Model--stages of change and decisional balance--as they relate to a new application in oral self-care behavior. An additional purpose was to determine if there was an association between these two components that would be applicable to a specific oral self-care behavior. METHODS: A three-part questionnaire was developed consisting of 1) stages of change instrument (4 items), 2) decisional balance instrument (40 items), and 3) demographic and dental experience information (9 items). Regular interdental cleaning was chosen as a behavior representing a commitment to oral self-care. The study population consisted of 709 subjects aged 35 to 55 who were recruited from 17 dental practices. RESULTS: A 70% (n = 521) response rate was obtained. Based upon the stages of change portion of the questionnaire, nearly 60% (n = 309) of the subjects were in the maintenance stage, while 21% (n = 109) were in precontemplation, with the rest distributed among the other stages. Reliability of the instrument was established with Kappa scoring. The decisional balance instrument was subjected to factor analysis resulting in a final decisional balance instrument of 28 items. There was a statistically significant relationship between the two components of stages of change and decisional balance. CONCLUSIONS: Stages of change and decisional balance instruments were developed and shown to be valid and reliable. Based upon the oral self-care behavior defined in this study, these instruments can identify an individual's current behavior and assess readiness to change by analyzing the distribution of the pros and cons a person considers when making a behavioral change. Understanding a client's behavioral stage would enable the practitioner to select and provide appropriate interventions. Further research should focus upon development of stage-appropriate intervention strategies and techniques, in order to move individuals along the continuum of stages toward behavioral change. Additionally, research with parallel and diverse populations is indicated.

Adult↗

Similarity searching in databases of three-dimensional molecules and macromolecules.

This paper discusses algorithmic techniques for measuring the degree of similarity between pairs of three-dimensional (3-D) chemical molecules represented by interatomic distance matrices. A comparison of four methods for the calculation of 3-D structural similarity suggests that the most effective one is a procedure that identifies pairs of atoms, one from each of the molecules that are being compared, that lie at the center of geometrically-related volumes of 3-D space. This atom mapping method enables the calculation of a wide range of types of intermolecular similarity coefficient, including measures that are based on physicochemical data. Massively-parallel implementations of the method are discussed, using the AMT Distributed Array Processor, that achieve a substantial increase in performance when compared with a sequential implementation on a UNIX workstation. Current work involves the use of angular information and the extension of the method to field-based similarity searching. Similarity searching in 3-D macromolecules is effected by the use of a maximal common subgraph (MCS) isomorphism algorithm with a novel, graph-based representation of the tertiary structures of proteins. This algorithm is being used to identify similarities between the 3-D structures of proteins in the Brookhaven Protein Data Bank; its use is exemplified by searches involving the NAD-binding fold motif.

Algorithms↗

Cool walking: a new Markov chain Monte Carlo sampling method.

Effective relaxation processes for difficult systems like proteins or spin glasses require special simulation techniques that permit barrier crossing to ensure ergodic sampling. Numerous adaptations of the venerable Metropolis Monte Carlo (MMC) algorithm have been proposed to improve its sampling efficiency, including various hybrid Monte Carlo (HMC) schemes, and methods designed specifically for overcoming quasi-ergodicity problems such as Jump Walking (J-Walking), Smart Walking (S-Walking), Smart Darting, and Parallel Tempering. We present an alternative to these approaches that we call Cool Walking, or C-Walking. In C-Walking two Markov chains are propagated in tandem, one at a high (ergodic) temperature and the other at a low temperature. Nonlocal trial moves for the low temperature walker are generated by first sampling from the high-temperature distribution, then performing a statistical quenching process on the sampled configuration to generate a C-Walking jump move. C-Walking needs only one high-temperature walker, satisfies detailed balance, and offers the important practical advantage that the high and low-temperature walkers can be run in tandem with minimal degradation of sampling due to the presence of correlations. To make the C-Walking approach more suitable to real problems we decrease the required number of cooling steps by attempting to jump at intermediate temperatures during cooling. We further reduce the number of cooling steps by utilizing "windows" of states when jumping, which improves acceptance ratios and lowers the average number of cooling steps. We present C-Walking results with comparisons to J-Walking, S-Walking, Smart Darting, and Parallel Tempering on a one-dimensional rugged potential energy surface in which the exact normalized probability distribution is known. C-Walking shows superior sampling as judged by two ergodic measures.

Journal Article↗

Cortical ultrastructure of Coleps bicuspis Noland, 1925 and the phylogeny of the class Prostomatea (Ciliophora).

The ultrastructure of Coleps bicuspis Noland, 1925 is described. The ciliate is a typical prostomate: the somatic kinetid is a monokinetid with a postciliary ribbon at triple 9, a kinetodesmal fibril originating near triplets 5, 6, 7 and an apparently radial transverse ribbon at triplet 4. The oral area is circular and has three brosse kineties associated with it. The brosse kineties are composed of dikinetids whose anterior kinetosome bears a tangential transverse ribbon and whose posterior kinetosome bears the fibrillar associates typical of a somatic monokinetid. The oral dikinetids are oriented parallel to the circumference of the oral cavity, which is surrounded by oral papillae and oral ridges. Pairs of nematodesmata, originating from oral dikinetid kinetosomes, are typically triangular in transection. A phylogeny of rhabdophoran ciliates is presented using the mixed parsimony algorithm and is discussed with reference to the systematic revisions of the phylum Ciliophora.

Animals↗

Spiral imaging: a critical appraisal.

In view of recent applications in cardiovascular and functional brain imaging, this work revisits the basic performance characteristics of spiral imaging in direct comparison to echo-planar imaging (EPI) and conventional rapid gradient-echo imaging. Using both computer simulations and experiments on phantoms and human subjects at 2.9 T, the study emphasizes single-shot applications and addresses the design of a suitable trajectory, the choice of a gridding algorithm, and the sensitivity to experimental inadequacies. As a general result, the combination of a spiral trajectory with regridding of the k-space data poses no principle obstacle for high-quality imaging. On the other hand, experimental difficulties such as gradient deviations, resonance offset contributions, and concomitant field effects cause more pronounced and even less acceptable image artifacts than usually obtained for EPI. Moreover, when ignoring parallel imaging strategies that are also applicable to EPI, improvements of image quality via reduced acquisition periods are only achievable by interleaved multishot spirals because partial Fourier sampling and rectangular fields of view (FOVs) cannot be exploited for non-Cartesian trajectories. Taken together, while spiral imaging may find its niche applications, most high-speed imaging needs are more easily served by EPI.

Algorithms↗