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PubMed1999

Amplitude of human head movements associated with horizontal saccades.

Human saccades may or may not be associated with head movements. To date, little attention has been devoted to the mechanisms determining head movement recruitment and scaling. Normal human subjects made horizontal, centrifugal saccades along an encircling array of light-emitting diodes. Measurements of gaze, head, and eye-in-head angle were made at the conclusion of the head movement (or at the end of the eye movement in eye-only saccades). We found that head movement amplitude (deltaH) related in a simple fashion to the eye eccentricity that would have resulted if the gaze shift had been performed without a head movement. Plots of deltaH vs this predicted eye eccentricity (E(PRED)) had a central flat region in which gaze shifts were unaccompanied by head movements (the eye-only range) and two flanking lobes in which deltaH was a linear function of E(PRED) (the eye-head ranges). DeltaH correlated with EPRED better than with gaze shift amplitude, as would be expected if head movements were controlled so as to keep eye eccentricity within a particular range. Head movement tendencies were quantified by the width of the eye-only range, the slope of the eye-head range, and the width of the region within which the eye was likely to be found at the conclusion of the completed gaze-shifting behavior (the customary ocular motor range). The measures ranged widely in these normal subjects: 35.8+/-31.9 degrees for the eye-only range (mean+/-SD), 0.77+/-0.16 for the slope of the eye-head range, and 44.0+/-23.8 degrees for the customary ocular motor range. Yet for a given subject, the measurements were reproducible across experimental sessions, with the customary ocular motor range being the most consistent measure of the three. The form of the deltaH vs E(PRED) plots suggests that the neural circuitry underlying eye-head coordination carries out two distinct functions--gating the head movement and scaling the head movement. The reason for the large intersubject variability of head movement tendencies is unknown. It does not parallel intersubject differences in full-scale eye (in orbit) range or full-scale neck range.

Adult↗
PubMedDate not supplied

Parallel computation of simple arithmetic using peptide-antibody interactions.

We propose a theoretical model for representing and manipulating binary numbers using peptide-antibody interactions. In particular, we present models to solve simple binary arithmetical problems like addition and subtraction. As the interactions can take place in parallel we show that the number of steps is independent of the size (bits) of the numbers.

Algorithms↗
PubMed2004

Analysis of perfect mappings of the stimuli through neural temporal sequences.

The analysis of an optimal neural system that maps stimuli into unique sequences of activations of fundamental atoms or functional clusters (FCs) is carried out. We say that it is perfect because the system maps with an injective function every stimulus in minimum time with the least number of FCs, such that every FC is activated only once. The neural system has the possibility to sustain several sequences in parallel. In this framework, we study the capacity achievable by the system, minimal completion time and complexity in terms of the number of parallel sequences. We show that the maximum capacity of the system is achieved without using parallel sequences at the expense of long completion times. However, when the capacity value is fixed, the largest possible number of parallel sequences is optimal because it requires short completion times. The complexity measure adds to important points: (i) the largest complexity of the system is achieved without parallel sequences, and (ii) the capacity estimation is a good estimation of the complexity of the system.

Algorithms↗
PubMedDate not supplied

Optimal design of protein production plants with time and size factor process models.

In this work we propose an optimization model for the design of a biotechnological multiproduct batch plant. A first level of detail posynomial model is constructed for each unit, as well as decisions regarding the structural optimization of the plant. A particular feature of this model is that it contains composite units in which semicontinuous items operate on the material contained by batch items. This occurs in the purification steps, in particular with the microfilters operating between retentate and permeate vessels, and with the homogenizer and ultrafilters operating on the material contained in a batch holding vessel. Also, the unit models rely on batch operating time expressions that depend on both the batch size and the size of semicontinuous items. The model takes into account all of the available options to increase the efficiency of the batch plant design: unit duplication in-phase and out-of-phase and intermediate storage tanks. The resulting mathematical model for the minimization of the plant capital cost is a mixed integer non-linear program (MINLP), which is solved to global optimality with an implementation of the outer approximation/ equality relaxation/ augmented penalty (OA/ER/AP) method. A plant that produces four recombinant proteins in eight processing stages is used to illustrate the proposed approach. An interesting feature of this example is that it represents an attempt to standardize a plant for the production of both therapeutic and nontherapeutic proteins; the model applied is generic and can thus be applied to any such modular plant. Results indicate that the best solution in terms of minimal capital cost contains no units in parallel and with intermediate storage tank allocation.

Algorithms↗
PubMed2002

Characterization of dose distributions through the max and mean dose concept.

A new approach for the determination of the equivalent uniform dose (EUD) for inhomogeneously irradiated normal organs is developed and tested. The EUD is calculated as a linear combination of the maximum and the mean dose: EUD = alphaDmax + (1 - alpha)D. We call this the max & mean model. The values of alpha are determined by a fit to the Emami tables for complication levels of 5% and 50%. The predictions of the max & mean model are compared with the Emami tables for different treatment volume fractions. The quality of the fit is also compared with the well-known power-law EUD model. The max & mean model makes it possible to make useful predictions of the EUD for organs having an organization anywhere between serial and parallel. The model can be fitted to the Emami tables within the same error range as the widely used power-law model (about 10%) and can be integrated into linear multicriteria optimization algorithms for planning of intensity-modulated radiotherapy.

Dose Fractionation, Radiation↗
PubMed2005

Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term.

BACKGROUND: Approximately 3% of children are born small for gestational age (SGA), and approximately 10% of SGA children maintain a small body size throughout childhood and often into adult life. Among short SGA children, growth hormone (GH) therapy increases short-term growth in a dose-dependent manner; experience with long-term therapy is limited. OBJECTIVE: To delineate the dose dependency of long-term height gain among short SGA children receiving GH therapy. METHODS: We performed an epianalysis of the first adult height data for SGA children (n = 28) enrolled in 3 randomized trials comparing the growth-promoting efficacy of 2 continuous GH regimens (33 or 67 microg/kg per day for approximately 10 years, starting at approximately 5 years of age); in addition, we performed a meta-analysis of the adult height results published previously and those presented here. RESULTS: Epianalysis outcomes (n = 28) suggested that adult height increased more with a higher-dose regimen than with a lower-dose regimen. In the meta-analysis (n = 82), the higher-dose regimen was found to elicit a long-term height gain superior to that achieved with the lower-dose regimen by a mean of 0.4 SD (approximately 1 inch). Children who were shorter at the start of therapy experienced more long-term height gain. CONCLUSIONS: These findings confirm GH therapy as an effective and safe approach to reduce the adult height deficit that short SGA children otherwise face. In addition, the first meta-analysis indicated that height gain is less dose dependent over the long term than over the short term, at least within the dose range explored to date. For SGA children whose stature is not extremely short, current data support the use of a GH dose of approximately 33 microg/kg per day from start to adult height, particularly if treatment starts at a young age; shorter children (for example, height below -3 SD) might benefit from an approach in which short-term catch-up growth is achieved with a higher dose (> or =50 microg/kg per day) and long-term growth to adult height is ensured with a GH dose of approximately 33 mug/kg per day. Because GH-induced accelerations of height and weight gain evolve in parallel, the dose tapering from > or =50 microg/kg to approximately 33 microg/kg can be accomplished by simply maintaining the absolute GH dose (in micrograms) while the child gains weight (in kilograms). With this algorithm, more growth-responsive children taper their GH dose down to approximately 33 microg/kg per day more quickly.

Adult↗
PubMed1994

[Parallel processing of dose calculation for external photon beam therapy].

We implemented external photon beam dose calculation programs into a parallel processor system consisting of Transputers, 32-bit processors especially suitable for multi-processor configuration. Two network conformations, binary-tree and pipeline, were evaluated for rectangular and irregular field dose calculation algorithms. Although computation speed increased in proportion to the number of CPU, substantial overhead caused by inter-processor communication occurred when a smaller computation load was delivered to each processor. On the other hand, for irregular field calculation, which requires more computation capability for each calculation point, the communication overhead was still less even when more than 50 processors were involved. Real-time responses could be expected for more complex algorithms by increasing the number of processors.

Mathematical Computing↗
PubMed2002

Modeling a parallel L4 neuron array of the fly (Musca domestica) vision system with a sequential processor.

At RMBS 2001 Olson presented a novel approach to image edge detection based on the vision system of the common house fly, Musca domestica [1]. Biologically based vision systems are inherently parallel and the vision related cells form a self-contained cartridge, ommatidium, which is duplicated across the surface of the fly's eye. Histological evidence provides the interconnection both within the vision cartridge and the connections to adjacent cartridges. Due to the parallel nature of biologically inspired vision systems, they outperform computer based digital vision systems in speed performance and memory requirements. Olson provided a model of the cartridge with its intra- and inter-connections. This model, rendered in MATLAB and Excel, demonstrated the feasibility of edge detection in the first several synaptic cellular connections within the cartridge. His results demonstrated how edge detection and object movements are easily obtained using a biologically based vision model. He demonstrated the model using simple rectangular and circular objects. We term this work Olson's Algorithm. We have extended Olson's Algorithm into a high-resolution model using a standard off-the-shelf frame grabber. Although, the frame grabber is a digitally based instrument, its image planes are used to model the photoreceptor layer (R1-R6), the L1, L2 monopolar cell layer, and also the monopolar L4 cell layer. The connections between these cells are programmed in "C". The high-resolution model demonstrates the feasibility of using a biologically based vision system in a real world application. Furthermore, it allows object segmentation, movement, and tracking to be modeled prior to implementation in parallel analog hardware.

Algorithms↗
PubMed2002

An atomically detailed study of the folding pathways of protein A with the stochastic difference equation.

An algorithm is applied here to compute folding pathways of staphylococcal protein A, fragment B. Emphasis is on studies of the complete process, starting from an ensemble of fully denatured conformations and ending at the folded state. The stochastic difference equation algorithm is based on optimization of an action that makes it possible to use a large integration step. Motions with typical displacements that change rapidly on the size scale of the step are filtered out, providing numerically stable and approximate solutions. The present approach is unique in maintaining an atomically detailed picture while providing a systematic, controlled approximation to the classical equations of motion. Analysis of 130 trajectories suggests the following folding mechanism for protein A: At an early precollapse phase of the process, a few native hydrogen bonds form near the C terminus of the protein. The hydrogen bonds are formed mostly within the third helix. The next step is chain collapse that occurs in parallel to additional growth of secondary structure seeds. Therefore, the present study does not support a pure hydrophobic collapse, or substantial early formation of secondary structure. At the last step, native tertiary contacts are formed at the same time as the completion of the secondary structure elements. To a large extent, the process is parallel and not sequential. The early formation of the third helix of protein A, fragment B (in the calculation), is consistent with experimental data.

Algorithms↗
PubMed2004

Monte Carlo-based treatment planning for a spoiler system with experimental validation using plane-parallel ionization chambers.

A beam spoiler is often used to increase the build-up dose near the surface for treatment of superficial treatment areas. Photon-beam spoilers produce a large amount of contaminant electrons, conditions for which standard, commercial treatment-planning system dose-calculation algorithms are inadequate for producing accurate dose calculations. In this study, we implemented a Monte Carlo (MC) dose-calculation algorithm for this spoiler system. With and without a spoiler of 1 cm Lucite, depth doses and transverse profiles in the build-up region were measured for field sizes of 5 x 5 cm2 and 10 x 10 cm2 at the spoiler-to-surface distances (STSDs) of 6, 10 and 15 cm. An Attix chamber and a Markus chamber were used for depth doses, whereas a diode detector was used for transverse profiles. An MC simulation using BEAM/DOSXYZ was used to compare the calculated and the measured data. The MC calculations agreed with the Attix chamber measurements within 2% for all STSDs and field sizes, whereas the Markus data--even with corrections made-showed a discrepancy of about 3.5% with a maximum difference of 7.3% for a field size of 10 x 10 cm2 at an STSD of 6 cm. The MC treatment-planning system was successfully applied to a head-and-neck case using 6 MV photon beams with a beam spoiler.

Algorithms↗
PubMed2004

A new hierarchical parallelization scheme: generalized distributed data interface (GDDI), and an application to the fragment molecular orbital method (FMO).

A two-level hierarchical scheme, generalized distributed data interface (GDDI), implemented into GAMESS is presented. Parallelization is accomplished first at the upper level by assigning computational tasks to groups. Then each group does parallelization at the lower level, by dividing its task into smaller work loads. The types of computations that can be used with this scheme are limited to those for which nearly independent tasks and subtasks can be assigned. Typical examples implemented, tested, and analyzed in this work are numeric derivatives and the fragment molecular orbital method (FMO) that is used to compute large molecules quantum mechanically by dividing them into fragments. Numeric derivatives can be used for algorithms based on them, such as geometry optimizations, saddle-point searches, frequency analyses, etc. This new hierarchical scheme is found to be a flexible tool easily utilizing network topology and delivering excellent performance even on slow networks. In one of the typical tests, on 16 nodes the scalability of GDDI is 1.7 times better than that of the standard parallelization scheme DDI and on 128 nodes GDDI is 93 times faster than DDI (on a multihub Fast Ethernet network). FMO delivered scalability of 80-90% on 128 nodes, depending on the molecular system (water clusters and a protein). A numerical gradient calculation for a water cluster achieved a scalability of 70% on 128 nodes. It is expected that GDDI will become a preferred tool on massively parallel computers for appropriate computational tasks.

Journal Article↗
PubMed2001

A theoretical evaluation of the assessment of effective dose using multiple personnel dosimeters.

The ability of a dose calculation algorithm, using the readings of multiple dosimeters, to accurately assess the effective dose under different photon irradiation conditions was assessed using computer simulation. The algorithm was that described in American National Standards Institute publication N13.41. Monte Carlo calculations with an anthropomorphic humanoid phantom were used to calculate the effective doses and also the expected readings of the multiple dosimeters. The irradiation geometries considered included a point source placed at several locations at a distance of 100 cm in front of the phantom, as well as an anterior-posterior plane parallel beam with a lead shield interposed between the phantom and the source. The point source energies considered were 0.05, 0.6, and 2 MeV, and the beam energy was varied between 0.03 and 10 MeV. Also considered were the estimates of effective dose based on the highest reading of the multiple dosimeters, a practice that is currently used in many work places. The results showed that use of the algorithm resulted in substantial improvements in the ability to accurately estimate effective dose. However, the results also showed that the improvements in accuracy were achievable only by using a calibration factor for the dosimetry that is different from the one obtained in current dosimetry calibration practices, and that without the use of this factor, the algorithm tended to underestimate the effective dose for nearly all the irradiation geometries considered. In addition, it appeared that this calibration factor is not constant but varies with irradiation conditions. There thus appears to be a problem of proper dosimetry calibration for use with the algorithm. This work considered only anterior posterior irradiations, and additional work is needed to assess the performance of the algorithm in other non-uniform irradiation geometries.

Algorithms↗
PubMed1988

Visual and auditory association areas of the cat's posterior ectosylvian gyrus: thalamic afferents.

The feline posterior ectosylvian gyrus contains a broad band of association cortex that is bounded anteriorly by tonotopic auditory areas and posteriorly by retinotopic visual areas. To characterize the possible functions of this cortex and to throw light on its pattern of internal divisions, we have carried out an analysis of its thalamic afferents. Deposits of differentiable retrograde tracers were placed at 17 cortical sites in nine cats. The deposit sites spanned the crown of the posterior ectosylvian gyrus and adjacent cortex in the suprasylvian sulcus. We compiled counts of retrogradely labeled neurons in 12 thalamic nuclei delineated by use of Nissl and acetylcholinesterase stains. We then employed a statistical clustering algorithm to identify groups of injections that gave rise to similar patterns of thalamic labeling. The results suggest that the posterior ectosylvian gyrus contains 3 fundamentally different cortical districts that have the form of parallel vertical bands. Very anterior cortex, overlapping previously identified tonotopic auditory areas (AI, P and VP) receives a dense projection from the laminated division of the medial geniculate body (MGl). An intermediate strip, to which we refer as the auditory belt, is innervated by axons from nontonotopic divisions of the medial geniculate body (MGds, MGvl, MGm, and MGd), from the lateral division of the posterior group (Pol), and from the posterior suprageniculate nucleus (SGp). A posterior strip, to which we refer as EPp, receives strong projections from the LM-SG complex (LM-SGa and LMp), and lighter projections from the intralaminar and lateroposterior (LPm and LPl) nuclei. On grounds of thalamic connectivity, EPp is not obviously distinguishable from adjacent retinotopic visual areas (PLLS, DLS, and VLS), and may be regarded as forming, together with these areas, a connectionally homogeneous visual belt.

Animals↗
PubMed2002

Identification of a novel class in the alpha/beta hydrolase fold superfamily: the N-myc differentiation-related proteins.

The alpha/beta hydrolases constitute a large protein superfamily that mainly consists of enzymes that catalyze a diverse range of reactions. These proteins exhibit the alpha/beta hydrolase fold, the essential features of which have recently been delineated: the presence of at least five parallel beta-strands, a catalytic triad in a specific order (nucleophile-acid-histidine), and a nucleophilic elbow. Because of the difficulties experimentally in identifying protein structures, we have used a Bayesian computational algorithm (PROBE) to identify the members of this superfamily based on distant sequence relationships. We found that the presence of five sequence motifs, which contain residues important for substrate binding and stabilization of the fold, are required for membership in this superfamily. The superfamily consists of at least 909 members, including the N-myc downstream regulated proteins, which are believed to be involved in cell differentiation. Unlike most of the other superfamily members, the N-myc downstream regulated proteins have never been proposed to possess the alpha/beta hydrolase fold and do not appear to be hydrolases.

Amino Acid Motifs↗
PubMed2005

Hardware-accelerated protein identification for mass spectrometry.

An ongoing issue in mass spectrometry is the time it takes to search DNA sequences with MS/MS peptide fragments (see, e.g., Choudary et al., Proteomics 2001; 1: 651-667.) Search times are far longer than spectra acquisition time, and parallelization of search software on clusters requires doubling the size of a conventional computing cluster to cut the search time in half. Field programmable gate arrays (FPGAs) are used to create hardware-accelerated algorithms that reduce operating costs and improve search speed compared to large clusters. We present a novel hardware design that takes full spectra and computes 6-frame translation word searches on DNA databases at a rate of approximately 3 billion base pairs per second, with queries of up to 10 amino acids in length and arbitrary wildcard positions. Hardware post-processing identifies in silico tryptic peptides and scores them using a variety of techniques including mass frequency expected values. With faster FPGAs protein identifications from the human genome can be achieved in less than a second, and this makes it an ideal solution for a number of proteome-scale applications.

Equipment Design↗
PubMed1989

A dosimetric comparison of three compensator design methods for the mantle field.

The mid-plane dose was measured in an anthropomorphic phantom for parallel opposed mantle fields as typically used in the treatment of Hodgkin's Disease. Doses were measured for four cases: no compensator, a compensator designed by a three-dimensional CT based treatment planning algorithm, a compensator designed from a port film, and a compensator designed from surface topography. The results showed all three compensators gave a significant better dose distribution than using no compensator at all. Without a compensator, doses varied from 92 percent to 131 percent, with a standard deviation of 10.9 percent for 65 measured points. The treatment planning algorithm gave the best performance with a standard deviation of 3.2 percent with all points but three within 5 percent out of the 65 points measured, and no points outside of 10 percent. The port film compensator was next best with a standard deviation of 4.4 percent, with 19 points outside of 5 percent, and doses from 88 to 106 percent. The surface topography compensator had a standard deviation of 6.1 percent with 31 points outside of 5% and doses from 89 to 114 percent.

Hodgkin Disease↗
PubMed2004

Detection of Mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system.

The use of volatile production patterns produced by Mycobacterium tuberculosis and associated bacterial infections from sputum samples were examined in vitro and in situ using an electronic nose based on a 14 sensor conducting polymer array. In vitro, it was possible to successfully discriminate between M. tuberculosis (TB) and control media, and between M. tuberculosis and M. avium, M. scrofulaceum and Pseudomonas aeruginosa cultures in the stationary phase after 5-6h incubation at 37 degrees C based on 35 samples. Using neural network (NN) analysis and cross-validation it was possible to successfully identify 100% of the TB cultures from others. A second in vitro study with 61 samples all four groups were successfully discriminated with 14 of 15 unknowns within each of the four groups successfully identified using cross-validation and discriminant function analysis. Subsequently, lipase enzymes were added to 46 sputum samples directly obtained from patients and the head space analysed. Parallel measurements of bacterial contamination were also carried out for confirmation using agar media. NN analysis was carried out using some of the samples as a training set. Based on the NN and genetic algorithms of up to 10 generations it was possible to successfully cross-validate 9 of 10 unknown samples. PCA was able to discriminate between TB infection alone, the controls, M. avium, P. aeruginosa and a mixed infection. These findings will have significant implications for the development of rapid qualitative systems for screening of patient samples and clinical diagnosis of tuberculosis.

Algorithms↗
PubMed2003

Quantitative classification and natural clustering of Caenorhabditis elegans behavioral phenotypes.

Genetic analysis of nervous system function relies on the rigorous description of behavioral phenotypes. However, standard methods for classifying the behavioral patterns of mutant Caenorhabditis elegans rely on human observation and are therefore subjective and imprecise. Here we describe the application of machine learning to quantitatively define and classify the behavioral patterns of C. elegans nervous system mutants. We have used an automated tracking and image processing system to obtain measurements of a wide range of morphological and behavioral features from recordings of representative mutant types. Using principal component analysis, we represented the behavioral patterns of eight mutant types as data clouds distributed in multidimensional feature space. Cluster analysis using the k-means algorithm made it possible to quantitatively assess the relative similarities between different behavioral phenotypes and to identify natural phenotypic clusters among the data. Since the patterns of phenotypic similarity identified in this study closely paralleled the functional similarities of the mutant gene products, the complex phenotypic signatures obtained from these image data appeared to represent an effective diagnostic of the mutants' underlying molecular defects.

Animals↗