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At least 19 recordsLinked to original sources
PubMed1999

Apparent fineness of stationary compound gratings.

Patterns consisting of the sum of a sinusoidal grating and its second spatial harmonic have an apparent spatial fineness, or periodicity, that is about halfway between the two component spatial frequencies. There are also phase dependent modulations of the apparent fineness about the mean fineness shift. Covariance between individuals' phase dependent fineness shifts indicates the presence of four spatial phase channels. The apparent fineness effects, and the putative phase channels, may both be a product of a local, linear, analysis of spatial frequency content. Illusory second harmonics, as generated in the spatial frequency doubling illusion, also change apparent fineness.

Contrast Sensitivity↗
PubMed1986

Biofeedback of visual evoked potentials.

The present study investigated the operant conditioning of visual evoked potentials within a latency range between 200 and 600 ms using a visual discrimination task, and scrutinized whether biofeedback-induced potential shifts covaried with behavioral responses (reaction time, RT). It could be demonstrated that subjects were able to modify their ERPs towards more or less positivity according to the instruction given. In addition, in could be shown that a biofeedback-induced greater positivity of the P300-complex was highly correlated with a decrease of reaction time. It is hypothesized that this could be due to a modification of P300-components reflecting information processing.

Adult↗
PubMed2025

Uncertainty Modeling Outperforms Machine Learning for Microbiome Data Analysis.

Microbiome sequencing measures relative rather than absolute abundances, providing no direct information about total microbial load. Normalization methods attempt to compensate, but rely on strong, often untestable assumptions that can bias inference. Experimental measurements of load (e.g., qPCR, flow cytometry) offer a solution, but remain costly and uncommon. A recent high-profile study proposed that machine learning could bypass this limitation by predicting microbial load from sequencing data alone. To evaluate this claim, we assembled mutt, the largest public database of paired sequencing and load measurements, spanning 35 studies and over 15,000 samples. Using mutt, we show that published machine learning models fail to generalize: on average they perform worse than a naive baseline that always predicted the training set mean. These failures stem from covariate shift-limited shared taxa between studies, differences in community composition, and differences in preprocessing pipelines-that silently derail model inputs. In contrast, Bayesian partially identified models do not attempt to impute microbial load, but instead propagate scale uncertainty through downstream analyses. Across 30 benchmark datasets, Bayesian partially identified models consistently outperformed normalization and machine learning approaches, providing a principled and reproducible foundation for microbiome inference.

16S rRNA-seq↗
PubMed1993

The influence of perceptual and motor factors on bimanual coordination in a polyrhythmic tapping task.

In this study the role of perceptual and motor factors on the motor organization (integrated versus parallel) adopted by musically skilled and unskilled subjects in a polyrhythmic tapping task was investigated. Subjects tapped a 3:2 polyrhythm to match the timing of two isochronous tone trains, one tone train for each hand. Perceptual factors were examined by the manipulation of the frequency difference between the tone trains to produce either an integrated or a streamed percept. Motor factors were examined by comparison of performance on two versions of the 3:2 polyrhythm. In one (simultaneous) version, each cycle of the polyrhythm began with a simultaneous left- and right-hand tap. In the other (shifted) version a 100-ms interval was introduced between the initial left and right taps in each cycle. Examination of the pattern of variances and covariances among intertap intervals suggested that most of the subjects in this study adopted an integrated motor organization that involved interleaving the timing of the two hands. Further analysis revealed that a serial chained model described the pattern of covariances best for the simultaneous pattern, whereas a hierarchical organization described the pattern of covariances for the shifted pattern best. The finding that performance was more accurate with integrated tones than with streamed tones provides some support for a perceptual-motor facilitation hypothesis.

Adult↗
PubMed2003

Interleukin-6 promoter haplotypes and interleukin-6 cytokine responses.

Genetic variations contribute to differences in the inflammatory response and are markers for disease risk and outcomes. We studied three single-nucleotide polymorphisms (-597 G-->A, -572 G-->C, and -174 G-->C) in the IL-6 promoter to determine associations with ex vivo LPS-stimulated IL-6 production by leukocytes. We also measured nuclear protein binding to synthetic oligonucleotides representing the -174 polymorphic region, located in proximity to important transcription factor motifs. We determined genotypes at three sites in the IL-6 promoter by pyrosequencing of genomic DNA obtained from 49 healthy control subjects. To determine molecular haplotypes, cloned DNA fragments from heterozygous subjects were sequenced. IL-6 release by whole blood leukocytes was measured after 24 h of ex vivo LPS stimulation. We compared IL-6 concentrations between haplotypes using Kruskall-Wallis and adjusted for covariates by analysis of covariance. Electromobility gel shift assay was carried out by the incubation of nuclear proteins from cultured human mononuclear cells with oligonucleotides representing the alternate -174 alleles. The amount of nuclear protein binding was quantified by densitometry, which was compared using analysis of variance. Genotype and sequence analysis of genomic and cloned DNA characterized three haplotypes. Ex vivo IL-6 production was greatest in individuals who were homozygous for the haplotype containing guanine at -597 and -174. IL-6 production was least for individuals homozygous for the haplotype containing adenine at -597 and cytosine at -174. Nuclear protein bound more avidly to guanine-containing oligonucleotides representing the -174 position than to oligonucleotides containing cytosine at that position. The IL-6 promoter haplotype influences ex vivo IL-6 response to endotoxin. This effect may be due to a functional effect of the -174 G-->C polymorphism.

Adult↗
PubMed1978

Changes of sensitivity to the cuing properties of narcotic drugs as evidenced by generalization and cross-generalization experiments.

With a discrete-trial, food-reward, two-lever procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. Individual threshold doses for generalization of fentanyl and for cross-generalization of morphine were determined repeatedly during a 17-week posttraining period. Threshold doses of both drugs almost continuously shifted in both the up- and downward direction. Shifts of fentanyl threshold doses covaried with those of morphine threshold doses. These shifts can best be described by a sustained oscillation, the mean amplitude of which amounts to a factor 3.65 of the dose-range for fentanyl, and to a factor 1.85 for morphine. The upper and lower limits of oscillation were symmetrical with respect to baseline. The oscillation can be described by a function expressing that the more distant a point along the function is from the baseline, the more it is susceptible to (positive/negative) acceleration along the intensity (i.e., dose) axis.

Animals↗
PubMed1982

Pure-tone anomalies. I. Pitch-intensity effects and diplacusis in normal ears.

Pitch-intensity functions were obtained in both ears of five normal-hearing subjects, together with measurements of binaural diplacusis as a function of intensity. The results show that pitch-intensity functions are often significantly different in the two ears of a given subject at a given frequency. Furthermore, for each subject and frequency condition tested, an intensity existed for which no significant diplacusis was found. For these conditions, therefore, binaural diplacusis as a function of intensity could be accounted for by the interaural differences in pitch-intensity functions. Forward-masking patterns (FMP's) as a function of intensity were also obtained in both ears of several subjects. The FMP's were compared with pitch-intensity functions, obtained for the same conditions, for evidence of a covariation in the direction of shifts in masking patterns as a function of intensity with the direction of pitch shifts as a function of intensity. No convincing evidence of such a covariation was found. The implications of the results of these experiments are discussed relative to the question of temporal versus tonotopic coding of pure-tone pitch.

Acoustic Stimulation↗
PubMed2001

Evidence that both ligand binding and covalent adaptation drive a two-state equilibrium in the aspartate receptor signaling complex.

The transmembrane aspartate receptor of bacterial chemotaxis regulates an associated kinase protein in response to both attractant binding to the receptor periplasmic domain and covalent modification of four adaptation sites on the receptor cytoplasmic domain. The existence of at least 16 covalent modification states raises the question of how many stable signaling conformations exist. In the simplest case, the receptor could have just two stable conformations ("on" and "off") yielding the two-state behavior of a toggle-switch. Alternatively, covalent modification could incrementally shift the receptor between many more than two stable conformations, thereby allowing the receptor to function as a rheostatic switch. An important distinction between these models is that the observed functional parameters of a toggle-switch receptor could strongly covary as covalent modification shifts the equilibrium between the on- and off-states, due to population-weighted averaging of the intrinsic on- and off-state parameters. By contrast, covalent modification of a rheostatic receptor would create new conformational states with completely independent parameters. To resolve the toggle-switch and rheostat models, the present study has generated all 16 homogeneous covalent modification states of the receptor adaptation sites, and has compared their effects on the attractant affinity and kinase activity of the reconstituted receptor-kinase signaling complex. This approach reveals that receptor covalent modification modulates both attractant affinity and kinase activity up to 100-fold, respectively. The regulatory effects of individual adaptation sites are not perfectly additive, indicating synergistic interactions between sites. The three adaptation sites at positions 295, 302, and 309 are more important than the site at position 491 in regulating attractant affinity and kinase activity, thereby explaining the previously observed dominance of the former three sites in in vivo studies. The most notable finding is that covalent modification of the adaptation sites alters the receptor attractant affinity and the receptor-regulated kinase activity in a highly correlated fashion, strongly supporting the toggle-switch model. Similarly, certain mutations that drive the receptor into the kinase activating state are found to have correlated effects on attractant affinity. Together these results provide strong evidence that chemotaxis receptors possess just two stable signaling conformations and that the equilibrium between these pure on- and off-states is modulated by both attractant binding and covalent adaptation. It follows that the attractant and adaptation signals drive the same conformational change between the two settings of a toggle. An approach that quantifies the fractional occupancy of the on- and off-states is illustrated.

Binding Sites↗
PubMed1980

Temperature-sensitive mutants of foot-and-mouth disease virus with altered structural polypeptides. II. Comparison of recombination and biochemical maps.

The structural polypeptides of foot-and-mouth disease virus were digested with Staphylococcus aureus V8 protease in the presence of sodium dodecyl sulfate. The protease-resistant peptides derived from temperature-sensitive mutants were compared with those of the wild type by electrofocusing in a polyacrylamide gel. Covariation between the charge shifts of different peptides indicated that they shared common sequences: only five independent peptides in all were derived from VP1, VP2, and VP3, accounting for approximately 50% of the polypeptide sequences. In two instances, amino acid substitutions that caused similar shifts in the isoelectric point were found to be located in different peptides. However, 15 mutants that possessed identical shifts in VP2 could not be distinguished by peptide analysis. The polypeptides of revertants able to grow at the nonpermissive temperature were compared with those of the parental mutants. By this test, 6 of the 12 distinguishable classes of coat protein mutations were found to covary with temperature sensitivity. In addition to true revertants, several phenotypic revertants which possessed a second charge change, either in a different structural polypeptide or in a different region of the same polypeptide, were isolated. The orientation of the recombination map was deduced from the loci of the coat protein mutations.

Amino Acid Sequence↗
PubMed2026

NoisyFlow: differentially private optimal transport using neural networks for secure biomedical data sharing across multiple institutions.

MOTIVATION: Biomedical models improve when trained on data pooled across institutions, but sensitive patient records (e.g. genomics, clinical data, and medical images) are difficult to share due to privacy constraints. Moreover, data collected at different sites often have shifted distributions because of covariate differences (including batch effects), so privacy-preserving sharing alone cannot simply resolve cross-site mismatch. Methods that protect individuals while explicitly aligning distributions are needed to enable reliable multi-institutional analyses. RESULTS: We present NoisyFlow, a three-stage differentially private framework for cross-institutional harmonization under distribution shift. In stage I, each site learns a differentially private flow-based generator of its local labeled distribution. In stage II, it learns a neural optimal transport map to a shared reference distribution. In stage III, a central server composes the released models to generate reference-aligned pseudo-data for downstream analysis without accessing raw records. Across four biomedical settings spanning single-cell genomics, histopathology, neurogenomics, and wearable sensing, NoisyFlow reduces distribution shift while preserving downstream utility under formal differential privacy guarantees. AVAILABILITY AND IMPLEMENTATION: The implementation of NoisyFlow is available at https://github.com/gersteinlab/NoisyFlow.

Information Dissemination↗
PubMed1998

Dynamic functional coupling of high resolution EEG potentials related to unilateral internally triggered one-digit movements.

Between-electrode cross-covariances of delta (0-3 Hz)- and theta (4-7 Hz)-filtered high resolution EEG potentials related to preparation, initiation. and execution of human unilateral internally triggered one-digit movements were computed to investigate statistical dynamic coupling between these potentials. Significant (P < 0.05, Bonferroni-corrected) cross-covariances were calculated between electrodes of lateral and median scalp regions. For both delta- and theta-bandpassed potentials, covariance modeling indicated a shifting functional coupling between contralateral and ipsilateral frontal-central-parietal scalp regions and between these two regions and the median frontal-central scalp region from the preparation to the execution of the movement (P < 0.05). A maximum inward functional coupling of the contralateral with the ipsilateral frontal-central-parietal scalp region was modeled during the preparation and initiation of the movement, and a maximum outward functional coupling during the movement execution. Furthermore, for theta-bandpassed potentials, rapidly oscillating inward and outward relationships were modeled between the contralateral frontal-central-parietal scalp region and the median frontal-central scalp region across the preparation, initiation, and execution of the movement. We speculate that these cross-covariance relationships might reflect an oscillating dynamic functional coupling of primary sensorimotor and supplementary motor areas during the planning, starting, and performance of unilateral movement. The involvement of these cortical areas is supported by the observation that averaged spatially enhanced delta- and theta-bandpassed potentials were computed from the scalp regions where task-related electrical activation of primary sensorimotor areas and supplementary motor area was roughly represented.

Adult↗
PubMed1989

Periodontal disease and oral microbial successions during myelosuppressive cancer chemotherapy.

Factors contributing to the succession of opportunistic pathogens at oral sites, including the periodontium, during myelosuppressive chemotherapy are poorly understood. This study examined the relation of periodontal disease to qualitative and proportional shifts in the oral microflora of 21 acute nonlymphocytic leukemia patients (7 male and 14 female, mean age (range) = 51.0 (25-81 years) observed during standardized myelosuppressive regimens. Supra- and subgingival microbial plaque specimens were individually collected from 2 contralateral oral sites (distobuccal of teeth 1-6 and 3-6) in each participant at hospital admission (day 1) and during point of maximal myelosuppression (day 14). Periodontal disease indices obtained at day 1 included site-specific measures of attachment loss and clinical assessment of disease status. Using a residualized change score analysis, periodontal disease status and attachment loss were positively correlated with increases in the proportional recovery of Staphylococcus sp. from supragingival sites and total yeast from supra- and subgingival sites. When age-related covariation in the microbial shifts was controlled in the analysis, periodontal disease status and attachment loss demonstrated no significant correlation with increases in total yeast at supragingival sites. These findings suggest that host factors such as periodontal disease may contribute to patterns of oral microbial successions during cancer chemotherapy.

Adult↗
PubMed1991

Temporal patterns of muscle activation for arm movements in three-dimensional space.

Little is known about the patterns of muscle activation that subserve arm movement in three-dimensional space. In this study, activation patterns of seven arm muscles were related to the spatial direction of human arm movement. Twenty movement directions defined two orthogonal vertical planes in space. The arm movements were moderately paced; each movement lasted approximately 500 msec. New techniques of EMG analysis were developed to describe the temporal pattern of muscle activation. For each muscle, a principal component analysis revealed a common phasic and tonic waveform for all directions of movement, within one plane. A temporal shifting procedure based on best covariance values revealed activation delays associated with different movement directions. The results show a consistent pattern of temporal shifting of the common waveform for movements in different directions. Coupled with past results showing that activation amplitude is a function of the cosine angle of movement or force direction, the present results suggest a relatively simple control strategy for mechanically complex arm movements: neural circuits produce a common phasic and tonic activation waveform that is scaled in amplitude and delayed in time, depending on the desired movement direction.

Arm↗
PubMed2000

Preparatory adjustments during gait initiation in 4-6-year-old children.

The preparatory adjustments related to gait initiation in a group of six children (4-6 years old) were studied in comparison to a group of six adults (50-61 years old). Muscle activity, ground reaction forces and body kinematics were recorded during the initiation of gait in subjects standing with one foot on each of two forceplates. Like adults, children had consistent anticipatory activations of the tibialis anterior (TA) muscle accompanied by center of pressure (COP) displacements, but the relative magnitude of both the backward COP displacement and concomitant initial TA activation burst were lower (P<0.03 and P<0.001 respectively) in children. The latter findings were associated with a lower rate of forward progression in children (P=0.01), and a lack of significant covariance between the backward shift and forthcoming velocity. In contrast, the preparatory adjustments in the medio-lateral (M/L) direction were prominent in children. Larger M/L peak force rates in children (P=0. 01) were associated with an earlier (P=0.007) weight transfer to the stance limb; moreover, children initiated gait from a wider (P=0.04) base of support and had a trajectory of the total COP that was lateral rather than posterior like in adults. The consistent preparatory adjustment responses indicate that the motor program for initiating gait is functional at this age. The prominence of the preparatory adjustments in the M/L direction together with a reduced magnitude of the responses in the antero-posterior direction suggest that the anticipatory behavior for initiating gait develops first in the frontal plane and that more walking experience and better postural stability are required to fully achieve the adult-like control of the gait initiation process.

Aging↗
PubMed1997

Development of spatial frequency tuned "covariance" channels: individual differences in the electrophysiological (VEP) contrast sensitivity function.

We investigated the spatial frequency tuned channels underlying the contrast sensitivity functions (CSFs) of adults and infants. CSFs were measured in adults and in 8-, 14-, 20-, and 32-week-old infants, using the swept-contrast visual evoked potential (sweep-VEP). At each age, 8 to 21 subjects provided complete data. Subjects viewed achromatic sine wave gratings (0.3 to 8 c/deg) on a 20 degrees field presented on a CRT. Gratings were counterphased at 12 reversals/s (6 Hz). The second harmonic response was used to interpolate thresholds. We computed statistical "sources" of individual variability (or factors) underlying CSFs, then calculated the number, nature (discrete vs. continuous) and frequency tuning of "covariance" channels. CSFs from adults each contained three spatial frequency tuned covariance channels, consistent with psychophysical results spanning a similar spatial frequency range. Covariance channels in infants shifted upward in spatial frequency with age, with rapid shifts occurring between 8 and 14 weeks. The change in scale coincided with, and was probably determined by, developmental cone migration into the fovea and growth in eye size.

Adult↗
PubMed1988

Superoxide dismutase conjugated to polyethylene glycol provides sustained protection against myocardial ischemia/reperfusion injury in canine heart.

Disagreement regarding the cardioprotective role of superoxide dismutase may relate to the use of different durations for induction of ischemic injury and reperfusion. The present study employed superoxide dismutase conjugated to polyethylene glycol (PEG-SOD), which has a half-life greater than 30 hours. Two protocols differing in the mode of administration and the duration of the reperfusion interval were used. Dogs were subjected to occlusion of the circumflex coronary artery for 90 minutes, then reperfused for 6 hours (Protocol A) or 4 days (Protocol B). The dogs received either polyethylene glycol conjugated to albumin (PEG-ALB) or PEG-SOD (1,000 U/kg). In Protocol A, treatment was administered starting 15 minutes before coronary occlusion and continued for 2 hours, terminating 15 minutes after reperfusion. Infarct size was determined 6 hours later. In Protocol B, the conjugated proteins were given 15 minutes before reperfusion and ended simultaneously with reperfusion. Infarct size was measured after 4 days. Infarct size (percentage of area at risk) in control (n = 9) and treated (n = 9) dogs in Protocol A differed between groups: 46.7 +/- 3.5% versus 28.3 +/- 2.9%, respectively (p less than or equal to 0.005); risk regions did not differ: 42.8 +/- 1.5% versus 43.8 +/- 2.1%, respectively. Myocardial salvage also was observed in Protocol B. Infarct size in control (n = 13) and treated (n = 13) groups was 44.2 +/- 2.6% versus 29.2 +/- 1.6%, respectively (p less than or equal to 0.005), with risk regions being 44.4 +/- 1.4% versus 46.0 +/- 1.6% (p = NS). Hemodynamic variables did not differ during the period of coronary artery occlusion. The respective collateral blood flows to the inner two thirds of the ischemic myocardium determined 60 minutes after occlusion were 0.05 +/- 0.01 ml/min/g and 0.06 +/- 0.04 ml/min/g (p = 0.806) for the PEG-ALB and PEG-SOD treated groups, respectively. Infarct size was related inversely to collateral blood flow in the PEG-ALB treated group. This relation shifted downward (analysis of covariance, p = 0.017). Plasma SOD activity in Protocols A sustained for 6 hours. Significant enzymatic activity was present after 4 days in Protocol B. Previous negative studies with native SOD may be related to the short half-life of its free-radical scavenging capacity, which compromises the chances of observing a protective effect after 4 days of reperfusion. The present results support our previous observations, as well as those of other investigators, demonstrating that superoxide dismutase can reduce that component of myocardial injury associated with reperfusion.

Animals↗
PubMed1996

Self-reported automobile accidents involving patients with obstructive sleep apnea.

We developed a routine survey instrument, which included data on self-reported motor vehicle accidents (MVA), among 253 patients who attended the UCLA Sleep Disorders Center to evaluate whether patients with diagnosed sleep apnea syndrome (SAS) have a higher ratio of MVAs. We used unconditional multiple logistic regression to determine the odds ratio between MVA and SAS, adjusted for the following covariates: age, sex, work shift, daytime nap, alcohol and coffee intake, and history of neurologic diseases. Thirty-one percent of patients with SAS compared with 15% of patients without SAS reported at least one MVA (p < 0.01). The adjusted odds ratio found through logistic multiple regression analysis was 2.99 (p < 0.01). The results demonstrate that patients with SAS had a higher ratio of self-reported MVA than did those without SAS and that the characteristics of falling asleep at inappropriate times and driving past destinations were two good indicators of probability of having an MVA. Nevertheless, sleep apnea is a very treatable condition; once treated the risk factors diminish considerably.

Accidents, Traffic↗
PubMed1988

Limitation of myocardial necrosis with verapamil during sustained coronary occlusion in the closed-chest dog.

Studies were undertaken to determine whether cardioprotection afforded by verapamil could be sustained in the dog heart during permanent coronary artery occlusion. In 48 dogs a coronary artery was occluded for 24 or 48 hours using a closed-chest embolization procedure. Dogs were assigned to either untreated control or to verapamil-treated (200 micrograms/kh, intravenous bolus within 5 minutes after coronary occlusion and then 5 micrograms/kg/min as a continuous intravenous infusion for 24 or 48 hours) groups. After 24 or 48 hours of permanent coronary occlusion, tissue necrosis was evaluated using tetrazolium staining and was related to the major baseline predictors of infarct size including anatomic risk zone (radiolabeled microsphere autoradiography) and coronary collateral flow. The correlation between infarct size and subepicardial coronary collateral flow was calculated in untreated control dogs (r = -0.91 and -0.80 for 24 and 48 hour controls, respectively); analysis of covariance indicated that verapamil treatment shifted this relation downward in both the 24- and 48-hour drug treatment groups. The equation of this regression was used to calculate the size of the infarct that would have occurred in treated dogs if drug treatment had not been initiated. The ratio of observed and calculated infarct size provides a "salvage index." In conclusion, verapamil was able to limit the extent of tissue necrosis and this cardioprotection appears to be sustained during 48 hours of permanent coronary occlusion.

Animals↗