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At least 1,693 records · Page 94Linked to original sources
PubMed1998

Effect of background components on spatial-frequency masking.

Previous studies of spatial-frequency masking and adaptation have shown that the contrast-detection threshold elevates maximally when the test spatial frequency is the same as the masking (or adapting) frequency but changes only slightly when they are separated by two or more octaves. At low spatial frequencies, however, the peak of the threshold-elevation function does not obey this rule: there is a well-established peak shift in the threshold-elevation functions toward higher spatial frequencies. We investigated whether this shift might be due to the masking effects caused by the background field, which contributes energy at the very low end of the spectrum. We first measured the effect of a 3-cycles/deg (c/deg) mask on detection of a range of test frequencies, compared with unmasked detection thresholds. We then measured the combined effect of a 2-c/deg and a 3-c/deg mask on detection, compared with detection with just the 2-c/deg mask. The comparison in the second case still tests the effect of the 3-c/deg mask, but the presence of the hidden 2-c/deg mask causes the peak masking effect to shift toward higher frequencies. This result provides a proof of concept for the hypothesis that the peak shift at low spatial frequencies is caused by the low-frequency energy in the background field, which is present in both masked and unmasked conditions. A five-parameter quantitative model of frequency masking is presented that describes the pure contrast-detection function, the frequency-masking functions at mask frequencies of 0.25, 0.5, 2, and 3 c/deg, and the peak-shift phenomenon.

Contrast Sensitivity↗
PubMed1992

Sites of age-related sensitivity loss in a short-wave cone pathway.

The age-related losses in the sensitivity of a short-wave (S) cone mechanism were determined by measuring the threshold-versus-radiance (t.v.r.) functions for nine older (mean age, 71.0 years) and six younger (mean age, 24.4 years) subjects. Measurements were obtained for a 250-ms, 1.03 degrees-diameter, 440-nm foveally viewed test light presented on 470-nm adapting fields and on a 570-nm auxiliary field. A comparison of t.v.r. functions revealed intensity-dependent sensitivity losses in the older group. By applying a quantitative model of an S-cone pathway to the t.v.r. data obtained from the older subjects, we found that the age-related changes in the ocular media and the receptor sensitivities can account for much but not all of the difference in the sensitivity of an S-cone mechanism demonstrated by eight of our nine older subjects.

Adolescent↗
PubMed2006

Adaptive control of laser modal properties.

An adaptive optical system for precise control of a laser beam's mode structure has been developed. The system uses a dynamic lens based on controlled optical path deformation in a dichroic optical element that is heated with an auxiliary laser. Our method is essentially aberration free, has high dynamic range, and can be implemented with high average power laser beams where other adaptive optics methods fail. A quantitative model agrees well with our experimental data and demonstrates the potential of our method as a mode-matching and beam-shaping element for future large-scale gravitational wave detectors.

Journal Article↗
PubMed2004

Quantitative analysis of Raman signal enhancement from aqueous samples in liquid core optical fibers.

Raman scattering from aqueous liquids can be collected with high efficiency by enclosing the liquid within a suitable waveguide, as several groups have reported. Here, we present a quantitative model that predicts the relative strength of signals collected from (a) a tubular waveguide and (b) a flat-walled cuvette. Experimental measurements of Raman scattering from aqueous ethanol are made using two geometries, a Teflon-AF waveguide and a standard quartz cuvette. The model correctly predicts the enhancements in several ethanol Raman bands provided by the waveguide geometry. This model should be useful in aligning and characterizing liquid core waveguides, whose manufacture is still undergoing refinements. In particular, the model shows that absorption and scattering losses affect the enhancement factor in different ways.

Bodily Secretions↗
PubMed2006

Noise-induced Min phenotypes in E. coli.

The spatiotemporal oscillations of the Escherichia coli proteins MinD and MinE direct cell division to the region between the chromosomes. Several quantitative models of the Min system have been suggested before, but no one of them accounts for the behavior of all documented mutant phenotypes. We analyzed the stochastic reaction-diffusion kinetics of the Min proteins for several E. coli mutants and compared the results to the corresponding deterministic mean-field description. We found that wild-type (wt) and filamentous (ftsZ-) cells are well characterized by the mean-field model, but that a stochastic model is necessary to account for several of the characteristics of the spherical (rodA-) and phospathedylethanolamide-deficient (PE-) phenotypes. For spherical cells, the mean-field model is bistable, and the system can get trapped in a non-oscillatory state. However, when the intrinsic noise is considered, only the experimentally observed oscillatory behavior remains. The stochastic model also reproduces the change in oscillation directions observed in the spherical phenotype and the occasional gliding of the MinD region along the inner membrane. For the PE- mutant, the stochastic model explains the appearance of randomly localized and dense MinD clusters as a nucleation phenomenon, in which the stochastic kinetics at low copy number causes local discharges of the high MinD(ATP) to MinD(ADP) potential. We find that a simple five-reaction model of the Min system can explain all documented Min phenotypes, if stochastic kinetics and three-dimensional diffusion are accounted for. Our results emphasize that local copy number fluctuation may result in phenotypic differences although the total number of molecules of the relevant species is high.

Adenosine Triphosphatases↗
PubMed2006

DARPP-32 is a robust integrator of dopamine and glutamate signals.

Integration of neurotransmitter and neuromodulator signals in the striatum plays a central role in the functions and dysfunctions of the basal ganglia. DARPP-32 is a key actor of this integration in the GABAergic medium-size spiny neurons, in particular in response to dopamine and glutamate. When phosphorylated by cAMP-dependent protein kinase (PKA), DARPP-32 inhibits protein phosphatase-1 (PP1), whereas when phosphorylated by cyclin-dependent kinase 5 (CDK5) it inhibits PKA. DARPP-32 is also regulated by casein kinases and by several protein phosphatases. These complex and intricate regulations make simple predictions of DARPP-32 dynamic behaviour virtually impossible. We used detailed quantitative modelling of the regulation of DARPP-32 phosphorylation to improve our understanding of its function. The models included all the combinations of the three best-characterized phosphorylation sites of DARPP-32, their regulation by kinases and phosphatases, and the regulation of those enzymes by cAMP and Ca(2+) signals. Dynamic simulations allowed us to observe the temporal relationships between cAMP and Ca(2+) signals. We confirmed that the proposed regulation of protein phosphatase-2A (PP2A) by calcium can account for the observed decrease of Threonine 75 phosphorylation upon glutamate receptor activation. DARPP-32 is not simply a switch between PP1-inhibiting and PKA-inhibiting states. Sensitivity analysis showed that CDK5 activity is a major regulator of the response, as previously suggested. Conversely, the strength of the regulation of PP2A by PKA or by calcium had little effect on the PP1-inhibiting function of DARPP-32 in these conditions. The simulations showed that DARPP-32 is not only a robust signal integrator, but that its response also depends on the delay between cAMP and calcium signals affecting the response to the latter. This integration did not depend on the concentration of DARPP-32, while the absolute effect on PP1 varied linearly. In silico mutants showed that Ser137 phosphorylation affects the influence of the delay between dopamine and glutamate, and that constitutive phosphorylation in Ser137 transforms DARPP-32 in a quasi-irreversible switch. This work is a first attempt to better understand the complex interactions between cAMP and Ca(2+) regulation of DARPP-32. Progressive inclusion of additional components should lead to a realistic model of signalling networks underlying the function of striatal neurons.

Basal Ganglia↗
PubMed2004

Pharmacogenetics of nicotine metabolism in twins: methods and procedures.

This article describes a pharmacogenetic investigation of nicotine metabolism in twins. One hundred and thirty-nine twin pairs (110 monozygotic and 29 dizygotic) were recruited and assessed for smoking status, zygosity, and health conditions known or suspected to affect drug metabolism. Participants underwent a 30-minute infusion of stable isotope-labeled nicotine and its major metabolite, cotinine, followed by an 8-hour in-hospital stay. Blood and urine samples were taken at regular intervals for analysis of nicotine, cotinine, and metabolites by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry and subsequent characterization of pharmacokinetic phenotypes. DNA was genotyped to confirm zygosity and for variation in the primary gene involved in nicotine metabolism, CYP2A6. Univariate and multivariate biometric analyses planned for the future will determine genetic and environmental influences on each pharmacokinetic measure individually and in combination with each other, and in the presence and absence of covariates, including measured genotype. When the analyses are completed, this study will result in a more complete characterization of the impact of genetic and environmental influences on nicotine and cotinine metabolic pathways than has heretofore been reported. The approach taken, with its use of a quantitative model of nicotine metabolism, highly refined metabolic phenotypes, measured genotype, and advanced tools for biometric genetic analysis, provides a model for the use of twins in next-generation studies of complex drug-metabolism phenotypes.

Adult↗
PubMed2006

Effects of bound ts3 on voltage dependence of sodium channel transitions to and from inactivation and energetics of its unbinding.

Recently, we proposed a quantitative model to explain the molecular mechanism of action of the Tityus serrulatus Ts3 alpha-toxin on sodium channels. In this model, the toxin acts as a stop that prevents the segment S4 of domain IV from reaching its outermost position, thus impairing the normal fast inactivation without affecting activation. In the present work, we analyze the predictions of the proposed model with regard to the voltage-dependent transitions to and from inactivation. Our results show that the recovery from inactivation was significantly faster in Ts3-bound channels and that there was no significant voltage dependence. The transition to inactivated state from open state in Ts3-modified channels presented a small but significant voltage dependence, which may derive from an intrinsic voltage dependence of inactivation or by a short movement of IVS4 in the presence of bound Ts3. We also studied the thermodynamic parameters of the voltage-dependent displacement of Ts3 from its binding site. We have observed that the activation energy to remove the toxin is 27 kJ/mol, part of which derives from the imposed depolarizing potential and the movement of an equivalent electrical charge of 0.54 e(0). These results support the proposed model.

Amino Acid Sequence↗
PubMed2006

BACE1 gene promoter is differentially regulated: detection of a novel promoter region for its cell type-specific regulation.

The amyloid-beta (Abeta) peptide, the proteolytic fragment of Abeta precursor protein (APP), aggregates and forms neuritic plaques, a major hallmark of Alzheimer's disease (AD). The limiting step in generating the Abeta peptide from APP is cleavage by the beta-secretase enzyme, BACE1. Regulation of the BACE1 gene is likely to play an important role in AD etiology and treatment. We therefore studied the activity of a 4.1-kb 5'-flanking region (-3765/+364, +1 being the transcription start site) of the BACE1 gene, both in 5'- and 3'-deletion series and through Northern blotting. We show that the BACE1 promoter has regulatory activity throughout the 4.1-kb length, both positive and negative, and that this activity can be quantitatively modeled according to promoter sequence length, with the specific model depending on the presence of negative regulatory elements as the 5'- most portion of the sequence. We also examined a previously identified 141-bp proximal fragment (+224/+364) of the BACE1 promoter and two constituent (91- and 50-bp) subfragments. We report that the 91-bp fragment (+224/+314) is the most likely seat of neuronal expression of the BACE1 gene and that it is the portion of the 141-bp fragment that accounts for observed DNA-protein interactions in brain extracts. The 50-bp fragment (+315/+364), which showed significant reporter gene activity from the empty vector, binds nuclear proteins in a cell type-specific manner and contains the AP2 site as shown by the electrophoretic mobility shift assay. Overall, the 141-bp fragment had no strong matches within GenBank, and the 91-bp fragment is predicted to have several potential stem-loop sites. Taken together, BACE1 gene promoter activity is differentially regulated, and the 91-bp fragment represents a novel promoter region for cell type-specific regulation. This fragment might be a useful target to regulate BACE1 expression leading to Abeta production and to understand the neuropathogenesis of AD.

Alzheimer Disease↗
PubMed2004

Genomic approaches in dissecting complex biological pathways.

Advances in genomic research have provided many types of large-scale data that contain rich information on various biological pathways. Intensive efforts have been made to qualitatively or quantitatively model biological pathways using these genomic data. Some general network properties, such as the scale-free property and network motifs, have been discussed and various network models have been applied to reconstruct pathways. However, there is a lack of systematic integration of prior knowledge and different genomic data in these analyses. In this review, we discuss pathway reconstruction under the consideration of the complexity embedded in the biological system, and the global and local properties of biological pathways. We review major methodologies, including clustering methods, scale-free networks models, Bayesian networks models, Boolean networks models, systems of differential equations, and data integration methods. We focus on the difficulty of each methodology in modeling biological pathways, and emphasize that different models capture different aspects of biological pathways or genomic data. The 'noisy' large-scale genomic data require the mathematical models and computational methods to be both robust and identifiable. In addition, we believe that ideal models should have the capability of incorporating various data types and these models need to be assessed through rigorous comparisons with empirical data.

Bayes Theorem↗
PubMed1998

A quantitative measure for degree of automation and its relation to system performance and mental load.

In this paper we quantitatively model degree of automation (DofA) in supervisory control as a function of the number and nature of tasks to be performed by the operator and automation. This model uses a task weighting scheme in which weighting factors are obtained from task demand load, task mental load, and task effect on system performance. The computation of DofA is demonstrated using an experimental system. Based on controlled experiments using operators, analyses of the task effect on system performance, the prediction and assessment of task demand load, and the prediction of mental load were performed. Each experiment had a different DofA. The effect of a change in DofA on system performance and mental load was investigated. It was found that system performance became less sensitive to changes in DofA at higher levels of DofA. The experimental data showed that when the operator controlled a partly automated system, perceived mental load could be predicted from the task mental load for each task component, as calculated by analyzing a situation in which all tasks were manually controlled. Actual or potential applications of this research include a methodology to balance and optimize the automation of complex industrial systems.

Adult↗
PubMed2005

Separate spatial scales determine neural activity-dependent changes in tissue oxygen within central visual pathways.

The relationship between oxygen levels and neural activity in the brain is fundamental to functional neuroimaging techniques. We have examined this relationship on a fine spatial scale in the lateral geniculate nucleus (LGN) and visual cortex of the cat using a microelectrode sensor that provides simultaneous colocalized measurements of oxygen partial pressure in tissue (tissue oxygen) and multiunit neural activity. In previous work with this sensor, we found that changes in tissue oxygen depend strongly on the location and spatial extent of neural activation. Specifically, focal neural activity near the microelectrode elicited decreases in tissue oxygen, whereas spatially extended activation, outside the field of view of our sensor, yielded mainly increases. In the current study, we report an expanded set of measurements to quantify the spatiotemporal relationship between neural responses and changes in tissue oxygen. For the purpose of data analysis, we develop a quantitative model that assumes that changes in tissue oxygen are composed of two response components (one positive and one negative) with magnitudes determined by neural activity on separate spatial scales. Our measurements from visual cortex and the LGN are consistent with this model and suggest that the positive response spreads over a distance of 1-2 mm, whereas the negative component is confined to a few hundred micrometers. These results are directly relevant to the mechanisms that generate functional brain imaging signals and place limits on their spatial properties.

Animals↗
PubMed2005

Visualization of synaptic vesicle movement in intact synaptic boutons using fluorescence fluctuation spectroscopy.

Not much is known about the mobility of synaptic vesicles inside small synapses of the central nervous system, reflecting a lack of methods for visualizing these dynamics. We adapted confocal spot detection with fluctuation analysis to monitor the mobility of fluorescently labeled synaptic vesicles inside individual boutons of cultured hippocampal neurons. Using Monte Carlo simulations we were able to propose a simple quantitative model that can describe vesicle mobility in small hippocampal boutons under resting conditions and different pharmacological treatments. We find that vesicle mobility in a time window of 20 s can be well described by caged diffusion (D approximately 5 x 10(-5) microm(2)/s, cage sizes of approximately 50 nm). Mobility can be upregulated by phosphatase blockage and increased further by actin disruption in a dose-dependent manner. Inhibition of the myosin light chain kinase slows down vesicle mobility 10-fold, whereas other kinases like protein kinase C (PKC), A (PKA), and calmodulin kinase II (caMKII) do not affect mobility in unstimulated boutons.

Actins↗
PubMed2001

The potential impact of bystander effects on radiation risks in a Mars mission.

Densely ionizing (high-LET) galactic cosmic rays (GCR) contribute a significant component of the radiation risk in free space. Over a period of a few months-sufficient for the early stages of radiation carcinogenesis to occur-a significant proportion of cell nuclei will not be traversed. There is convincing evidence, at least in vitro, that irradiated cells can send out signals that can result in damage to nearby unirradiated cells. This observation can hold even when the unirradiated cells have been exposed to low doses of low-LET radiation. We discuss here a quantitative model based on the a formalism, an approach that incorporates radiobiological damage both from a bystander response to signals emitted by irradiated cells, and also from direct traversal of high-LET radiations through cell nuclei. The model produces results that are consistent with those of a series of studies of the bystander phenomenon using a high-LET microbeam, with the end point of in vitro oncogenic transformation. According to this picture, for exposure to high-LET particles such as galactic cosmic rays other than protons, the bystander effect is significant primarily at low fluences, i.e., exposures where there are significant numbers of untraversed cells. If the mechanisms postulated here were applicable in vivo, using a linear extrapolation of risks derived from studies using intermediate doses of high-LET radiation (where the contribution of the bystander effect may be negligible) to estimate risks at very low doses (where the bystander effect may be dominant) could underestimate the true risk from low doses of high-LET radiation. It would be highly premature simply to abandon current risk projections for high-LET, low-dose radiation; however, these considerations would suggest caution in applying results derived from experiments using high-LET radiation at fluences above approximately 1 particle per nucleus to risk estimation for a Mars mission.

Animals↗
PubMed2005

Relationships between Cd and Zn partitioning and geochemical composition in sediments from Chinese rivers.

Adsorption isotherm experiments were conducted to determine the distribution coefficients (Kd) for Cd and Zn between water and sediments from twelve rivers in eastern China. The low metal concentration (<10(-10) M) added into the sediment-water system enabled the direct measurements of linear adsorption isotherms. When other solution parameters, such as ionic strength, were controlled, sediment geochemical characteristics were the major factors affecting metal distribution. The Kd was highly dependent on the total organic carbon contents and Fe-Mn oxide at pH = 7.0, and was affected significantly by the carbonate content in the sediments due to its control of pH. The Kd of the Huanghe sediments, which had the highest carbonate concentration (13.1%), increased sharply for both Cd and Zn when the pH increased. A quantitative model using the experimentally obtained phase distribution coefficients (Kd)i was applied to study the effects of different geochemical phases in the sediment on metal distributions. The (Kd)i of carbonate was correlated significantly with the carbonate content in the sediment, whereas the (Kd)i of total organic carbon (TOC) and Fe-Mn oxide phases were highly pH dependent. Using the (Kd)i for each geochemical phase, the calculation showed that about 91% and 85% of sorbed Cd and Zn, respectively, added to the batch reactors were distributed among the three major geochemical phases: TOC, Fe-Mn oxide, and carbonate. Total organic carbon was the most important binding phase for Cd, and Fe-Mn oxide for Zn. Furthermore, adsorption experiments with simulated sediments show the importance of interactions between different geochemical phases on metal partitioning.

Animals↗
PubMed1978

Conservation, choice, and the concurrent fixed-ratio schedule.

Five rats got all of their water in daily 60-minute sessions. Two levers and a water spout were freely available throughout baseline sessions. Contingency sessions offered a choice between two alternative fixed-ratio components, in the form of a choice between the two levers. Each component required a specified number of lever presses for access to the spout, and then a specified number of licks for another choice between components. Given the observed relative frequency, the absolute frequency of selecting each component was predicted accurately by assuming that the subject conserved between baseline and contingency the total amount of a dimension attributable to lever pressing and licking. Several quantitative models for predicting relative frequency were examined. The best of these assumed that the subject would show a nonexclusive preference for the component requiring fewer lever presses.

Journal Article↗
PubMed1989

Choice and terminal-link response topography.

Six pigeons responded under concurrent-chains schedules. For 3 birds, pecking was required in both initial links; for 3 others, treadle pressing was required. For all subjects, pecking was required in one terminal link and treadling in the other. The initial links consisted of independent variable-interval 60-s schedules. All birds were exposed to five pairs of terminal-link variable-interval schedules over 10 conditions: 6 s versus 54 s, 18 s versus 42 s, 30 s versus 30 s, 42 s versus 18 s, and 54 s versus 6 s. Comparisons of responding under nominally identical terminal-link variable-interval schedules showed that, without exception, higher choice proportions were obtained for the alternative correlated with terminal-link pecking. Moreover, terminal-link delay to reinforcement was shorter for terminal-link pecking than for terminal-link treadling chains. This factor, along with response force requirements, was implicated in explaining the present as well as previous findings of preference for pecking over treadling. It was found also that the delay-reduction hypothesis provided only a moderately accurate description of performance under concurrent chains in which different terminal-link response topographies are required. These findings suggest that quantitative models neglecting the effects of differing terminal-link topographies may be incomplete.

Journal Article↗
PubMed1994

Effects of qualitatively different reinforcers on the parameters of the response-strength equation.

This experiment examined the relationship between two qualitatively different reinforcers and the parameters of a quantitative model of reinforced responding, referred to as the response-strength equation or the Herrnstein equation. A group of rats was first food deprived and later water deprived. An 11.5% sucrose solution served as the reinforcer in the food-deprivation condition, and water was the reinforcer in the water-deprivation condition. Each experimental session consisted of a series of seven variable-interval schedules, providing reinforcement rates that varied between 20 and 1,200 reinforcers per hour. The response rates increased in a negatively accelerating function in a manner consistent with the response-strength equation. This equation has two fitted parameters, k and Re. According to one theory, the k parameter is a measure of motor performance, and Re is indicative of the relative reinforcement efficacy of the background uncontrollable sources of reinforcement in relation to the experimentally arranged reinforcer. In this study, k did not change as a result of the different reinforcers, but Re was significantly larger in the sucrose-reinforcement condition. These results are consistent with the interpretation that k and Re measure two independent and experimentally distinguishable parameters and provide further evidence that absolute response rate is a function of relative reinforcement rate, as implied by the derivation of the response-strength equation based on the matching law.

Animals↗