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PubMed1992

A new motion responsive pacemaker: first clinical experience with an acceleration sensor pacemaker.

A new accelerometer-based adaptive rate pacemaker (EXCEL VR) was evaluated to investigate its behavior at nominal settings during treadmill exercise testing and postural changes. Eight patients with sinus rhythm were selected to compare intrinsic heart rate to sensor mediated rate. Throughout exercise treadmill testing, changes in the sensor mediated rate closely paralleled actual physiological changes. The Pearson product moment correlation of pacing rate with sinus frequency, calculated for all patients, was r = 0.82 (P = 0.001). Change in the patient's physical position resulted in immediate change in sensor rate, which corresponded appropriately to the type of position change and activity level. Average (+/- SD) pacing rate was 62.4 +/- 2.7 beats/min supine; 67 +/- 3.8 beats/min sitting; 69.8 +/- 6.4 beats/min standing; 81.6 +/- 8.7 beats/min slow walking; and 96.8 +/- 1.3 beats/min fast walking. After 4 minutes of recovery, the average pacing rate dropped to 65 +/- 3 beats/min. The interaction between the accelerometer and the pulse generator at nominal settings was accurate and infrequently required the use of its many programming options. The accelerometer sensor and pulse generator algorithm in this device during postural change and exercise resulted in physiological-like changes in sensor mediated heart rate.

Acceleration↗
PubMed1987

Two-dimensional 1H NMR study of human ubiquitin: a main chain directed assignment and structure analysis.

The 1H resonances of human ubiquitin were studied by two-dimensional nuclear magnetic resonance techniques. A recently introduced assignment algorithm termed the main chain directed (MCD) assignment [Englander, S. W., & Wand, A. J. (1987) Biochemistry 26, 5953-5958] was applied. This approach relies on an ordered series of searches for prescribed patterns of connectivities in two-dimensional J-correlated and nuclear Overhauser effect spectra and centers on the dipolar interactions involving main-chain amide NH, alpha-CH, and beta-CH. Unlike the sequential assignment procedure, the MCD approach does not rest upon definition of side-chain J-coupled networks and is generally not sequential with the primary sequence of the protein. The various MCD patterns and the general algorithm are reiterated and applied to the analysis of human ubiquitin. With this algorithm, the vast majority of amino acid residue amide NH-C alpha H-C beta H J-coupled subspin systems could be associated with and aligned within units of secondary structure without any knowledge of the identity of the side chains. This greatly simplified recognition of side-chain spin systems by restricting their identity. Essentially complete resonance assignments are presented. The MCD method is compared with the sequential assignment method in some detail. The MCD method is highly amenable to automation. Human ubiquitin is found, at pH 5.8 and 30 degrees C, to be composed of an extensive beta-sheet structure involving five strands. Three of these strands form an antiparallel set sharing a common strand and have a parallel orientation to two antiparallel strands. Two helical segments were also observed. The largest, spanning 13 residues, shows dipolar interactions consistent with an alpha-helix while the smaller 4-residue helical segment appears, on the basis of observed nuclear Overhauser effects, to be a 3(10) helix. Five classical tight turns could be demonstrated.

Humans↗
PubMed2026

Atlas-level single-cell integration and clustering-free differential expression analysis with GEDI 2.0.

MOTIVATION: GEDI is a generative framework for multi-sample, multi-condition single-cell analysis that performs batch correction, latent representation learning, and clustering-free differential expression within a unified model. However, the original implementation suffered from prohibitive memory use and runtime, preventing its application to modern atlas-scale datasets. RESULTS: We present GEDI 2.0, a complete high-performance reimplementation featuring a standalone C++ computational core with pre-allocated workspaces, strict sparse-matrix preservation, optimized BLAS routines, and multi-threaded block-coordinate descent. Across extensive benchmarks spanning up to 500 000 cells and 10 000 features, GEDI 2.0 achieves 40%-63.6% mean reduction in peak memory, 2.98× mean single-threaded speedups, and up to 11.5× acceleration with parallel execution, while maintaining full numerical equivalence to the original method. These improvements enable GEDI 2.0 to analyze million-cell datasets, a scale not achievable with the legacy implementation. GEDI 2.0 provides R and Python interfaces and seamless interoperability with common single-cell workflows. AVAILABILITY AND IMPLEMENTATION: Source code, documentation, reproducible codebase, and tutorials are available at https://github.com/csglab/gedi2.

Single-Cell Analysis↗
PubMedDate not supplied

Appraising the instantaneous secretory rates of luteinizing hormone and testosterone in response to selective mu opiate receptor blockade in late pubertal boys.

The pulsatile properties of gonadotropin and testosterone release were examined before and after chronic mu opiate receptor blockade with naltrexone, 50 mg every other day, in four normal boys in late puberty (ages 14 8/12 to 15 1/12 years). The nature of spontaneous secretory events was appraised for immunoactive LH and testosterone in blood withdrawn every 20 minutes for 24 hours, using a novel, discrete deconvolution algorithm to estimate apparent instantaneous secretory rates. The application of this methodology revealed that the frequency of discrete LH instantaneous secretory rates increased after mu opiate receptor blockade (P = 0.011). More strikingly, all parameters of testosterone secretory events responded significantly to mu opiate receptor blockade, including increases in mean estimated secretory rate (+47%, P = 0.02), testosterone pulse frequency (+ 64%, P less than 0.001) and amplitude (+ 20%, P = 0.027). Correspondingly, decreases in testosterone interpulse secretory intervals (-35%, P = 0.001), secretory pulse duration (-19%, P = 0.042) and interpulse valley duration (-35%, P = 0.006) also were noted. There was a prominent diurnal rhythm in testosterone secretion with maximal values in the morning and late evening, and marked reductions in the afternoon, sometimes to prepubertal levels. This variation in the testosterone secretory profile paralleled that of LH. In response to naltrexone, the FSH concentration series showed a significant increase in the mean FSH concentration (+ 18%) P = 0.003) and mean peak amplitude (+ 15%, P = 0.002). These data provide indirect evidence of functional coupling of the opiate system with the hypothalamic GnRH pulse generator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Distributed parallel processing in the vertical vestibulo-ocular reflex: learning networks compared to tensor theory.

The vestibulo-ocular reflex (VOR) is capable of producing compensatory eye movements in three dimensions. It utilizes the head rotational velocity signals from the semicircular canals to control the contractions of the extraocular muscles. Since canal and muscle coordinate frames are not orthogonal and differ from one another, a sensorimotor transformation must be produced by the VOR neural network. Tensor theory has been used to construct a linear transformation that can model the three-dimensional behavior of the VOR. But tensor theory does not take the distributed, redundant nature of the VOR neural network into account. It suggests that the neurons subserving the VOR, such as vestibular nucleus neurons, should have specific sensitivity-vectors. Actual data, however, are not in accord. Data from the cat show that the sensitivity-vectors of vestibular nucleus neurons, rather than aligning with any specific vectors, are dispersed widely. As an alternative to tensor theory, we modeled the vertical VOR as a three-layered neural network programmed using the back-propagation learning algorithm. Units in mature networks had divergent sensitivity-vectors which resembled those of actual vestibular nucleus neurons in the cat. This similarity suggests that the VOR sensorimotor transformation may be represented redundantly rather than uniquely. The results demonstrate how vestibular nucleus neurons can encode the VOR sensorimotor transformation in a distributed manner.

Animals↗
PubMed1992

Limitations of Augustinsson plots.

The Augustinsson plot transforms the Michaelis-Menten equation by graphing velocity, v, as a function of velocity/substrate, v/s. The plot is linear with a negative slope for a single class of saturable sites and curvilinear for multiple classes of sites. Statistically, Augustinsson plots suffer from the limitation that there is no true independent variable. Experimental errors form a Gaussian distribution that rests neither parallel to the v axis nor v/s axis, but rather along a line emanating from the origin. Widening the range of s values produces increasingly large errors in the calculated Km and Vm values, especially when multiple sites are present. Exact data containing no error produces accurate constants using either the Michaelis-Menten or Augustinsson equation. With Km and Vm constants previously derived by fitting data with the statistically valid Michaelis-Menten equation, the Augustinsson plot may be used accurately to display multiple site data.

Algorithms↗
PubMedDate not supplied

Effects of high-dose medroxyprogesterone acetate and various other steroid hormones on plasma membrane lipid mobility in CAMA-1 mammary cancer cells.

The influence of medroxyprogesterone acetate (MPA) and various other steroid hormones on the lateral diffusion of the fluorescent lipid probe 1-acyl-2-(N-4-nitrobenzo-2-oxa-1.3-diazolyl)-aminocarpropylphos phatidylcholine (NBD-PC) in the plasma membrane of intact mammary cancer cells (CAMA-1 cell line) has been studied by fluorescence recovery after photobleaching technique. Incubation of cells with MPA in serum free medium at ambient temperature for 1 hr led to a significant decrease in the lateral diffusion coefficient of NBD-PC. MPA induced this change over a limited concentration range with 10(-7)-10(-5) mol/l near-maximal or maximal effects, and 10(-8) mol/l exhibiting no effect. Exposure of the CAMA-1 cells to 10(-7) mol/l MPA in undiluted serum induced a significant effect following 1.5 hr of treatment with no increase in effectiveness up to 4 hr of incubation. As compared to MPA, the other steroids tested were less effective or ineffective. The influence on lateral lipid mobility diminished as follows: MPA greater than progesterone greater than 5a-DHT approximately 17 beta-estradiol greater than dexamethasone, and roughly seems to parallel their lipid solubility as estimated by partition coefficients in an n-octanol-water system. Any involvement of classical steroid hormone receptors in the mechanism of membrane action could be excluded. Nongenomic steroid effects on the plasma membrane are assumed. As the structure and function of biomembranes are modulated by lipid-bilayer fluidity and membranes crucially participate in nearly all aspects of cell biology, it is concluded that direct interactions of MPA with membranes potentially play a role in the antitumor activity of the compound.

Algorithms↗
PubMed2026

SNaQ.jl: Improved scalability for level-1 phylogenetic network inference.

MOTIVATION: Phylogenetic networks represent complex biological scenarios that are overlooked in trees, such as hybridization and horizontal gene transfer. Although numerous methods have been developed for phylogenetic network inference, their scalability is severely limited by the computational demands of likelihood optimization and the vastness of network space. Composite (or pseudo-) likelihood approaches like SNaQ have improved computational tractability for network inference, but they remain inadequate for datasets of sizes routinely handled by tree inference methods. RESULTS: Here, we introduce SNaQ.jl, a new standalone Julia package with the composite likelihood inference originally implemented within PhyloNetworks.jl as well as new scalability features that enhance computational efficiency through (i) parallelization of quartet likelihood calculations during composite likelihood computation, (ii) weighted random selection of quartets, and (iii) probabilistic decision-making during network search. Through a simulation study and empirical data analysis, we show that this new version of SNaQ.jl (version 1.1) improves average runtimes by up to 499% on average with no change in function parameters or method accuracy. AVAILABILITY AND IMPLEMENTATION: SNaQ.jl is a new open source Julia package available at https://github.com/JuliaPhylo/SNaQ.jl.

Phylogeny↗
PubMedDate not supplied

MR color mapping of myelin fiber orientation.

Diffusion of water in brain white matter has been shown to be anisotropic: Water mobility is lower when measured perpendicular to the fiber direction rather than parallel to it. This feature was used to produce images of the myelin fiber orientation. Coronal and sagittal MR diffusion images were obtained in volunteers using an echo-planar imaging sequence sensitized to molecular diffusion in perpendicular directions. Color-coded images of myelin orientation were then generated by combining these images together. The orientation of the white matter tracts was found to be in excellent agreement with known anatomy. Myelin fiber orientation mapping may offer a new perspective to evaluate white matter disorders.

Algorithms↗
PubMed1992

Evidence for a generalized Laguerre transform of temporal events by the visual system.

It is generally assumed that the early visual processing is constituted by a set of filters operating in parallel. In this respect the visual system performs a transform, generating a code of the characteristics of the input signal. Recently, it has been suggested that the coding of the spatial characteristics by the visual system can be described by a Hermite transform (Martens, 1990a, b). It was also suggested that a three-dimensional Hermite transform can be used to code spatiotemporal events. In contrast to this latter suggestion, we argue that the coding of temporal events takes the form of a generalized Laguerre transform. We review psychophysical evidence supporting this hypothesis.

Algorithms↗
PubMed1987

HOMED: a homologous sequence editor.

The alignment of homologous sequences with each other and their display has proved a difficult task, despite a frequent requirement for this process. HOMED enables related sequences to be edited and listed in parallel with each other. The editor function uses a full screen editor which emulates the text editors KED and EDT (on PDP-11 and VAX-11 respectively) and which can be adapted to emulate other text editors. This emulation has been adopted to simplify user learning of editing functions. HOMED provides functions for listing the sequences in a variety of formats and for generating a consensus sequence as well as providing a series of tools for maintenance of the sequence database. HOMED has been implemented in Pascal in a modular fashion to enhance portability.

Algorithms↗
PubMedDate not supplied

Simultaneous reconstruction, segmentation, and edge enhancement of relatively piecewise continuous images with intensity-level information.

A multinomial image model is proposed which uses intensity-level information for reconstruction of contiguous image regions. The intensity-level information assumes that image intensities are relatively constant within contiguous regions over the image-pixel array and that intensity levels of these regions are determined either empirically or theoretically by information criteria. These conditions may be valid, for example, for cardiac blood-pool imaging, where the intensity levels (or radionuclide activities) of myocardium, blood-pool, and background regions are distinct and the activities within each region of muscle, blood, or background are relatively uniform. To test the model, a mathematical phantom over a 64 x 64 array was constructed. The phantom had three contiguous regions. Each region had a different intensity level. Measurements from the phantom were simulated using an emission-tomography geometry. Fifty projections were generated over 180 degrees, with 64 equally spaced parallel rays per projection. Projection data were randomized to contain Poisson noise. Image reconstructions were performed using an iterative maximum a posteriori probability procedure. The contiguous regions corresponding to the three intensity levels were automatically segmented. Simultaneously, the edges of the regions were sharpened. Noise in the reconstructed images was significantly suppressed. Convergence of the iterative procedure to the phantom was observed. Compared with maximum likelihood and filtered-backprojection approaches, the results obtained using the maximum a posteriori probability with the intensity-level information demonstrated qualitative and quantitative improvement in localizing the regions of varying intensities.

Algorithms↗
PubMed1990

Tomography using a rotating slant-hole collimator and a large number of projections.

A tomographic method using a limited-view angle has been evaluated. In studies using a gamma camera and a rotating 30-degree slant-hole (RSH) collimator, 64 projection images were registered. A special filtered backprojection technique was used for reconstruction of section images parallel to the collimator face. Resolution within such sections was 0.6 cm, 3 cm from the collimator face and 1.3 cm at 18 cm. Depth resolution was 2.2 cm at 3 cm and 5.1 cm at 18 cm. Spacing between section images was regular and geometric distortion negligible. Short-axis section images of a myocardium in vivo were qualitatively comparable or better than those obtained with single-photon emission computed tomography. Degradation in the posterior wall due to attenuation and scatter was less. Section images of the facial bones and a hip joint further demonstrated the tomographic capability of the method.

Algorithms↗
PubMedDate not supplied

Cranial CT artifacts and gantry angulation.

Computed tomographic investigation of the brain is frequently accomplished by scanning parallel to the canthomeatal line. In these scans, evaluation of the brain stem and neighboring structures is often compromised by streak artifacts from bone-induced beam hardening. These artifacts may be reduced by introducing a change in gantry angulation. Results from a phantom study as well as from a clinical trial offer evidence that may be helpful in assessing different scanning planes. An inclination of 5 degrees below Reid baseline is suggested to minimize the interpetrous artifact. Variations in slice thickness and exposure parameters do not appear to affect significantly this typical posterior fossa artifact.

Algorithms↗
PubMed1987

Kinetics of reactivation during refolding of guanidine-denatured pancreatic ribonuclease A.

The method aforementioned (Liu, W. and Tsou, C.L. (1987) Biochim. Biophys. Acta 916, 455-464) for the study of the kinetics of irreversible modification of enzyme activity has been applied to the reactivation of guanidine-denatured ribonuclease A, by following the hydrolysis of cyclic CMP during refolding upon diluting a guanidine-denatured enzyme with a substrate-containing buffer. Appropriate equations have been derived to deal with the kinetics of the substrate reaction during the course of activation, while the product formed, 3'CMP, is a competitive inhibitor. When the overall process consists of multiple first-order reactions, the individual rate constants could be obtained by suitable semilogarithmic plots. Moreover, in certain cases, it can be distinguished from the shapes of the plots, whether the overall process consists of parallel or consecutive first-order reactions. The kinetics for the reactivation reaction has been compared to that for the refolding of the substrate binding site, as indicated by complex formation with the competitive inhibitor, 2'CMP, and for the refolding of the molecule as a whole. At pH 6.0 and 25 degrees C, only monophasic first-order reactions could be detected by manual mixing for both the reactivation and the refolding processes. At lower temperatures (0-10 degrees C), both processes consist of two first-order reactions. In all cases, the same rate constants have been obtained for the refolding and reactivation reactions.

Algorithms↗
PubMed1992

The amplitude and periodicity of synchronized renal sympathetic nerve discharges in anesthetized cats: differential effect of baroreceptor activity.

We applied a computerized peak detection algorithm to recordings of synchronized sympathetic nerve discharges from anesthetized cats to retrieve information about the characteristics of renal nerve activity (RNA) during changes in baroreceptor activity. The algorithm scanned the series of RNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RNA peak had been detected, its corresponding amplitude, width and peak-to-peak interval were calculated. The peak-to-peak interval periodicity showed two modes of synchronized discharge, one between 200-500 ms accounting for 47% of intervals, and a higher 20-180 ms frequency (49% of intervals). Baroreceptor stimulation decreased the occurrence of the high frequencies while increasing the probability of the lower frequency components. The overall occurrence of synchronized peaks per second fell linearly to zero with increases in blood pressure. The peak amplitude of RNA was unimodally distributed and was not affected by baroreceptor stimulation until an increase in mean arterial pressure reached a threshold (mean 142 +/- 5 mmHg) whereupon it fell quickly to zero. Sino-aortic vagal denervation did not affect the distribution of peak height. The width of synchronized discharges was also unimodal, mean 82 +/- 1 ms, and was almost unchanged during baroreflex stimulation acting in parallel with changes in the peak amplitude and decreasing at high blood pressures. Sino-aortic vagal denervation did not affect the synchronized width. There was no relationship between the periodicity and amplitude or width of synchronized discharges under all conditions. The results indicate that the periodicity and amplitude of renal synchronized discharges appear to be independent of each other and are differentially affected by baroreceptor input.

Animals↗
PubMedDate not supplied

A study of interface effects in 60Co beams using a thin-walled parallel plate ionization chamber.

A large plane-parallel ionization chamber has been constructed to investigate interface effects in 60Co beam. The designed geometry yields negligible perturbation from the side walls, as opposed to the large effects existing in commercially available plane-parallel chambers. The chamber has been used to investigate interface phenomena in transition zones using a wide range of elements (Z = 4-82) as front- and back-scattering media and a clinically relevant 60Co gamma-ray field size. The effects of varying the chamber height discretely (0.5-11 mm) and increasing the wall thickness (1-9 mg/cm2) have been investigated. The variation of the measured ionization with the experimental setup (air gap between backscatter material and chamber wall, measurements at dmax and at 5-cm depth, varying the material both in front of and behind the chamber, etc.) has also been investigated. The simple geometry of the ion chamber has been found optimum for benchmark studies of Monte Carlo calculations. The ion chamber is suited for investigating experimentally the effects of varying transport parameters used in Monte Carlo simulations. The results presented show that the complex physical mechanisms governing 60Co interface dosimetry still make Monte Carlo condensed-history (macroscopic) techniques uncertain. It has been found that the EGS4 Monte Carlo system, together with the user code DOSRZ V4.0 and the PRESTA algorithm, yields good agreement with experiments for low and medium Z (main interest in dosimetry and radiotherapy), but may underestimate up to 10% the backscatter from high-Z materials even when transport parameters are optimized.

Algorithms↗
PubMed1988

Topographic relations between ocular dominance and orientation columns in the cat striate cortex.

In the visual cortex of four adult cats ocular dominance and orientation columns were visualized with (3H)proline and (14C)deoxyglucose autoradiography. The two columnar systems were reconstructed from serial horizontal sections or from flat-mount preparations and graphically superimposed. They share a number of characteristic features: In both systems the columns have a tendency to form regularly spaced parallel bands whose main trajectory is perpendicular to the border between areas 17 and 18. These bands frequently bifurcate or terminate in blind endings. The resulting irregularities are much more pronounced in the ocular dominance than in the orientation system. The periodicity of the columnar patterns was assessed along trajectories perpendicular to the main orientation of the bands and differed in the two columnar systems. The spacing of the ocular dominance stripes was significantly narrower than the spacing of orientation bands. The mean periodicity of a particular columnar system was virtually identical in the two hemispheres of the same animal but it differed substantially in different animals. However, the spacing of orientation columns covaried with that of the ocular dominance columns, the ratios of the mean spacings of the two columnar systems being similar in the four cats. The superposition of the two columnar systems revealed no obvious topographic relation between any of the organizational details such as the location of bifurcations, blind endings and intersections. We suggest the following conclusions: 1. The developmental processes generating the two columnar systems seem to obey the same algorithms but they act independently of each other. 2. The space constants of the two systems are rigorously specified and appear to depend on a common variable. 3. The main orientation of the bands in both columnar systems is related to a) the representation of the vertical meridian, b) the anisotropy of the cortical magnification factor, and c) the tangential spread of intracortical connections.

Animals↗