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Tomographic time-of-flight optical imaging device.

Time-resolved optical imaging has been used to image phantoms, animals, and humans, and offers the potential for the production of functional images of human tissues, such as the oxygenation of brain during stroke. We had previously reported a transmission scanner, and now give an early report on conversion to a rotational tomographic scanner with a non-parallel ray geometry similar to early CAT scanners. Initial scans show that 1) spatial imaging in turbid media using time-of-flight measurements, non-recursive algorithms, and standard tomographic geometry is possible, 2) separation of absorbance and scattering as an image is attainable, a key step in performing spatially-resolved chemometric analysis, 3) imaging of multiple objects buried within scattering material is feasible, demonstrating that equations derived for homogeneous media can be applied in at least some cases to inhomogeneous media such as tissue-like phantoms, and 4) imaging of brain pathology produces recognizable images with sufficient resolution for diagnostic decisions. We conclude that optical tomography is feasible for clinical use and that conversion of the present mechanically scanning device to a clinical scanner should be possible with retention of the current processing algorithms. Such a clinical scanner should ultimately be able to generate images in a few minutes with centimeter resolution at the center of living human brain.

Algorithms↗

Celloidin mounting (embedding without infiltration) - a new, simple and reliable method for producing serial sections of high thickness through complete human brains and its application to stereological and immunohistochemical investigations.

Celloidin mounting (embedding without infiltration) of the human central nervous system (CNS) proved to be superior to gelatin embedding for the production of serial sections ranging in thickness from 220 to 500 microm. After gallocyanin-staining, a comprehensive neuroanatomical as well as neuropathological survey of the human brain is possible, including diagnosis of Alzheimer's disease. Details of a fractionator analysis of the total striatal neuron number are described and the possible quantitative analysis of parallel immunohistochemically stained sections is discussed.

Adult↗

The free energy landscape for beta hairpin folding in explicit water.

The folding free energy landscape of the C-terminal beta hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and OPLSAA force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME/RESPA. The simulation results show that the hydrophobic core and the beta strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The beta hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.

Amino Acid Sequence↗

Identification of K(+) channels in the plasma membrane of maize subsidiary cells.

The stomatal complex of Zea mays consists of two guard cells with the pore in between them and two flanking subsidiary cells. Both guard cells and subsidiary cells are important elements for stoma physiology because a well-coordinated transmembrane shuttle transport of potassium and chloride ions occurs between these cells during stomatal movement. To shed light upon the corresponding transport systems from subsidiary cells, subsidiary cell protoplasts were enzymatically isolated and in turn, analyzed with the patch-clamp technique. Thereby, two K(+)-selective channel types were identified in the plasma membrane of subsidiary cells. With regard to their voltage-dependent gating behavior, they may act as hyperpolarization-dependent K(+) uptake and depolarization-activated K(+) release channels during stomatal movement. Interestingly, the K(+) channels from subsidiary cells and guard cells similarly responded to membrane voltage as well as to changes in the K(+) gradient. Further, the inward- and outward-rectifying K(+) current amplitude decreased upon a rise in the intracellular free Ca(2+) level from 2 nM to the micro M-range. The results indicate that the plasma membrane of subsidiary cells and guard cells has to be inversely polarized in order to achieve the anti-parallel direction of K(+) fluxes between these cell types during stomatal movement.

Algorithms↗

Calculation of the uncertainty in the dose delivered during radiation therapy.

There is, inevitably, uncertainty in our knowledge of the dose at any point within an irradiated patient. A technique is presented for estimating this uncertainty by performing three parallel calculations, one using nominal values and the others extreme values of the parameters upon which the dose depends. Such calculations can be made with almost any algorithm for calculating dose. They result in an estimate, at some specified confidence level which is determined by the data used, of the range of dose likely at any point. Such calculations should help therapists to avert over- or underdosage which might not be evident in conventional calculations of the nominal dose.

Humans↗

Magnocellular pathway for rotation invariant Neocognitron.

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

Algorithms↗

Multigrid approach to predictive wave-front reconstruction in adaptive optical systems.

A computationally efficient approach, based on the principles of multigrid methods, to predictive wave-front reconstruction in adaptive optical systems is described. Local predictive estimators are computed by use of recursive least squares on multiple grids. Each grid is increasingly coarse, allowing for temporal prediction of the behavior of both high- and low-spatial-frequency aberrations. Example numerical simulation results are given, showing that implementing the recursive least-squares algorithm for predictive estimation in a multigrid fashion greatly accelerates convergence to the steady-state optimal estimator condition. By implementation of the multigrid predictive reconstructor in parallel, the computational cost of implementing a predictive wave-front reconstruction scheme that uses recursive least squares for each processor at each cycle can be reduced from [symbol: see text](m2) to [symbol: see text](2m), where m is the number of actuators.

Journal Article↗

Compensation of distant phase-distorting layers. II. Extended-field-of-view adaptive receiver system.

We analyze the anisoplanatic adaptive receiver system field of view (FOV) and the possibility of controlling the system FOV by using an adaptive optics system with multiple wave-front sensors that sense wave-front phase aberrations of reference waves with different arrival angles. The conventional decoupled stochastic parallel gradient descent (D-SPGD) technique is generalized to include output signals from multiple wave-front sensors. The multiple-reference D-SPGD control algorithm introduced here is applied to obtain an anisotropic FOV in adaptive receiver systems by using two and three reference waves.

Journal Article↗

Effect of the signal-to-noise ratio on the quality of linear estimation reconstructions of distributed current sources.

Currently, linear estimation reconstruction is the only feasible method for extracting information about spatially distributed current sources from measurements of neural magnetic fields. We present the results of a systematic study of the effect of the signal-to-noise ratio on the imaging quality of one such algorithm in over-as well as undetermined circumstances. In particular, we will discuss the necessary trade-off between the contradictory goals of a minimum norm of the reconstructed current density distribution and of a minimal deviation of the reconstructed fields from the measured fields. As an example, we show the reconstruction of a simple arrangement of two nearly parallel dipoles in two different depths inside a spherical volume conductor, discussing the differences between the computer simulation without noise and simulation with a realistic noise level.

Algorithms↗

A restoration algorithm for P-32 and Y-90 bremsstrahlung emission nuclear imaging: a wavelet-neural network approach.

A novel wavelet-based neural network (WNN) filter is proposed for image restoration as required for imaging of beta emitters by bremsstrahlung detection using a gamma camera. Quantitative imaging of beta emitters is important for the in vivo management of antibody therapy using either P-32 or Y-90. The theoretical basis for the general case for M-channel multiresolution wavelet decomposition of the nuclear image into different subimages is developed with the objective of isolating the signal from noise. A modified Hopfield neural network (NN) architecture is then used for multichannel image restoration using the dominant signal subimages. The NN model avoids the common inverse problem associated with other image restoration filters such as the Wiener filter. The relative performance of the WNN for image restoration, for M = 2 channel, is compared to a previously reported order statistic neural network hybrid (OSNNH) filter. Initially simulated degraded images of known structures with different noise levels are used. Quantitative metrics such as the normalized mean square error (NMSE) and signal-to-noise ratio (SNR) are used to compare filter performance. The WNN yields comparable results for image restoration with suggested slightly better performance for the images with higher noise levels as often encountered in bremsstrahlung detection. Attenuation measurements were performed using two radionuclides, 32P and 90Y as required for calibration of the gamma camera for quantitative measurements. Similar values for an effective attenuation coefficient were observed for the restored images using the OSNNH filters (32P: mu = 0.122 cm-1, 90Y: mu = 0.135 cm-1) and WNN (32P: mu = 0.122 cm-1, 90Y: mu = 0.135 cm-1) filters with slightly higher values obtained for the raw data (32P: mu = 0.142 cm-1, 90Y: mu = 0.142 cm-1) for a 3.5-cm source size. The WNN, however, was computationally more efficient by a factor of 4 to 6 compared to the OSNNH filter. The filter architecture, in turn, is also optimum for parallel processing or VLSI implementation as required for planar and particularly for SPECT mode of detection.

Algorithms↗

Order-disorder phenomena in myelinated nerve sheaths. I. A physical model and its parametrization: exact and approximate determination of the parameters.

An algorithm is developed for the analysis of the X-ray scattering spectra of lamellar systems, by reference to a precise physical model. The model consists of identical planar lamellae (the motif), all parallel and stacked in a one-dimensional crystal with four types of defect: stacking disorder, finite size of the crystallites, and presence of diffuse and blank scattering. In addition, the spectra are distorted by collimation aberrations. In order to evaluate the effects of these distortions, the following assumptions are made: (1) beyond some point Slimit the intensity curve can be expressed as a function of a (small) number of parameters; (2) the blank scattering, restricted to very small angles, can be identified and eliminated; and (3) the diffuse scattering is entirely defined by the values of idiff(h/D) at the lattice Sh = h/D (h is a positive integer less than or equal to DSlimit). These assumptions lead to an expression of the whole of the intensity curve as a function of a finite number of parameters: the average D and the variance sigma 2D of the repeat distance, the average number [N] of lamellae per crystallite, the set [idiff(h/D)] and the set [imotif(k/2D)] (where k is a positive integer), which defines the structure of the motif. An algorithm is proposed to determine the value of the various parameters. The derivation of the algorithm involves several operations: construction in real space of periodic functions whose motifs are step-sections of the autocorrelation function; expression in reciprocal space, and in terms of the experimental scattering curves, of the Fourier transform of those periodic functions; analysis of the properties of the two functions. The algorithm is tested using a variety of simulated scattering curves whose parameters [imotif(k/2D)], [idiff(2/D)], D, sigma D, [N] (and collimation distortions) are within the range commonly encountered in experimental conditions. The results show that the values of the parameters retrieved by the algorithms are very close to those used in the simulation. The calculations are fast and easy to implement on a computer. The main virtues of the algorithm are (1) to determine the values of all the parameters at once, eliminating most of the intermediate (and questionable) manipulations (separation of signal from noise, discrimination of overlapping reflections, integration of the intensities) and (2) to yield the continuous intensity curve of a single motif.

Algorithms↗

Arbitrary oblique image sections for 3-D radiation treatment planning.

Methods for selecting and computing arbitrary image sections for displaying anatomic and isodose information for three-dimensional treatment planning are investigated. Selection of the desired plane may be made by defining a plane that is perpendicular to an existing image section (called the base image) and passing through a line on the base image. Alternatively, the anatomic structures displayed perspectively in three dimensions as a series of contours that can be rotated and translated may be used to define an arbitrary plane for image reconstruction. The viewing screen is considered to be the plane of interest. As a typical three-dimensional image of 30 to 60 sections requires considerable computer storage (on the order of 25 megabytes), a reconstruction algorithm may need extensive memory space or CPU and disk I/O time. Of the schemes examined, we believe the following is the most efficient. One pair of images is read from the disk at a time in sequence and intersections of the rows of the cutting plane with the box formed by the consecutive images are computed. Pixel values of all points between the given images are computed by interpolation. Special cases, such as the cutting plane being parallel to or coincident with an existing image, must be considered separately.

Algorithms↗

EEG noise cancellation by a subspace method based on wavelet decomposition.

BACKGROUND: Noise reduction techniques play an essential role in EEG signal processing applications. A variety of methods are currently in use, including those based on linear filtering and adaptive noise cancellation, as well as subspace-based methods using singular value decomposition (SVD). SVD offers a robust method to decompose the data matrix into signal and noise subspaces. However, the SVD algorithm is characterized by high computational complexity, which restricts its use in real time EEG signal analysis. MATERIAL/METHODS: In this work we applied a wavelet transform to decompose the EEG signal into parallel subsignals. Noise was cancelled using the SVD-based method for each subsignal, and the noiseless EEG was reconstructed by using an inverse wavelet transform. EEGs were recorded in freely behaving rats from two different sites of the brain: 1). the hilar region of the dentate gyrus of the hippocampus, 2). the frontal cortex, with the electrode tip located in the vicinity of the epipial neocortical surface. RESULTS: Our noise suppression method had the most obvious effect on the EEG frequency spectrum, where random noise was considerably diminished. In the time domain, the reconstructed waveform closely resembled the original EEG signal, but it could clearly be seen that most of the transient spikes had been removed. CONCLUSIONS: The present method offers remarkable computational savings and is especially well adapted for the analysis of highly dynamic EEGs.

Algorithms↗

Computer models of DNA four-way junctions.

A modeling scheme that combines a constrained backbone generating algorithm with simple hard-sphere packing calculations is offered to build the four-stranded structures of DNA found in Holliday junctions. Two standard B-DNA duplexes are oriented side by side with helix axes at different relative inclinations and then systematically rotated and translated to identify closely spaced contact-free states. Attempts are subsequently made to introduce a low-energy sugar-phosphate linkage that serves as the site of strand exchange between the two duplexes. The chemical connection is sought using an algorithm which identifies the possible arrangements of the intervening backbone torsions between arbitrarily positioned bases. The goal is to identify the multiple conformational solutions associated with a particular arrangement of neighboring DNA helices in the four-way junction rather than a single optimum structure. The methodology is general, in terms of accommodating four-way junctions with arms of variable conformation and chain length and of dimensions much greater than treated heretofore. The only deformation in the four-way structures relative to B-DNA occurs at the site of backbone exchange, with base stacking and Watson-Crick pairing completely preserved in all models. The arrangements of neighboring bases at these sites resemble the unusual conformational steps found in a number of small molecule nucleic acid crystal structures. An interesting outcome of the calculations is the formation of sterically acceptable four-arm Holliday junctions over a wide range of angles at the cross. The potential mobility of the Holliday junctions is inferred from visualization and energetic analysis of the various models. Long-range electrostatic energies based on different currently available treatments of the dielectric constant are used to estimate the conformational preferences and flexibility of the four-stranded structures. The various dielectric schemes, however, are not in complete agreement on the likely conformational variability of the four-way junctions. The structures suggest a possible mechanism for branch migration and detail a pathway linking the antiparallel uncrossed Holliday structure inferred from solution measurements and the parallel cross-packed helical arrangements observed in single-crystal X-ray studies.

Algorithms↗

CD8 T-cell recognition of human 5T4 oncofetal antigen.

The 5T4 oncofetal antigen is expressed by a wide variety of human carcinomas, including colorectal, ovarian and gastric carcinomas. The restricted expression of 5T4 on tumor tissues as well as its implication in tumor progression and bad prognosis makes 5T4 a promising new candidate for immunotherapy. An MVA vaccine encoding 5T4 antigen has been successfully evaluated in preclinical studies in a murine tumor model. Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4). Analysis of several donors confirms a repertoire of such CD8 responses. In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen. Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFN gamma ELISPOT. Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA. Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response. In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.

Adenoviridae↗

Generalized eigenvector algorithm for nonlinear system identification with non-white inputs.

Traditional methods for nonlinear system identification require a white, Gaussian, test input, a restriction that has limited their usability in many fields. In this study, we address the problem of identifying the dynamics of a nonlinear system when the input is highly colored-a restriction commonly encountered in the study of physiological systems. An extension of the parallel cascade method is developed that is optimal in a constrained minimum mean squared error sense and exactly corrects for the distortion induced by the non-white input spectrum. However, this correction is a deconvolution, which may become extremely ill-conditioned if the input spectrum departs significantly from whiteness; to confront this, we develop a low-rank projection operation that stabilizes the deconvolution. The overall algorithm is robust and places few requirements on the nature of the test input. Practical application of this new method is demonstrated by using it to identify a known analog nonlinear system from experimental data.

Algorithms↗

The exponential edge-gradient effect in x-ray computed tomography.

The exponential edge-gradient effect must arise in any x-ray transmission CT scanner whenever long sharp edges of high contrast are encountered. The effect is non-linear and is due to the interaction of the exponential law of x-ray attenuation and the finite width of the scanning beam in the x-y plane. The error induced in the projection values is proved to be always negative. While the most common effect is lucent streaks emerging from single straight edges, it is demonstrated that dense streaks from pairs of edges are possible. It is shown that an exact correction of the error is possible only under very special (and rather unrealistic) circumstances in which an infinite number of samples per beam width are available and all thin rays making up the beam can be considered parallel. As a practical matter, nevertheless, increased sample density is highly desirable in making good approximate corrections; this is demonstrated with simulated scans. Two classes of approximate correction algorithms are described and their effectiveness evaluated on simulated CT phantom scans. One such algorithm is also shown to work well with a real scan of a physical phantom on a machine that provides approximately four samples per beam width.

Humans↗

Dynamic ion channel activation scheduling in patch clamp on a chip.

In 2002, Fertig et al. made a remarkable invention: the first successful demonstration of a patch clamp on a chip--a planar quartz-based biological chip that contains up to several hundred ion channels. This patch-clamp chip can be used in massively parallel screens for ion channel activity, thereby providing a high-throughput screening tool for drug discovery efforts. In this paper, we propose computationally efficient dynamic stochastic scheduling algorithms for activating individual ion channels in the patch-clamp chip. By formulating the ion channel activation scheduling problem as a partially observed Markov decision process with a multiarmed bandit structure, near-optimal dynamic scheduling for activation of the individual channels is achieved to optimize the information gained from the patch-clamp chip. Numerical examples using state-of-the-art algorithms developed recently in artificial intelligence and operations research are presented to illustrate these dynamic ion channel (macromolecule) activation scheduling algorithms.

Algorithms↗