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PubMed2006

Frequency domain analysis of noise in simple gene circuits.

Recent advances in single cell methods have spurred progress in quantifying and analyzing stochastic fluctuations, or noise, in genetic networks. Many of these studies have focused on identifying the sources of noise and quantifying its magnitude, and at the same time, paying less attention to the frequency content of the noise. We have developed a frequency domain approach to extract the information contained in the frequency content of the noise. In this article we review our work in this area and extend it to explicitly consider sources of extrinsic and intrinsic noise. First we review applications of the frequency domain approach to several simple circuits, including a constitutively expressed gene, a gene regulated by transitions in its operator state, and a negatively autoregulated gene. We then review our recent experimental study, in which time-lapse microscopy was used to measure noise in the expression of green fluorescent protein in individual cells. The results demonstrate how changes in rate constants within the gene circuit are reflected in the spectral content of the noise in a manner consistent with the predictions derived through frequency domain analysis. The experimental results confirm our earlier theoretical prediction that negative autoregulation not only reduces the magnitude of the noise but shifts its content out to higher frequency. Finally, we develop a frequency domain model of gene expression that explicitly accounts for extrinsic noise at the transcriptional and translational levels. We apply the model to interpret a shift in the autocorrelation function of green fluorescent protein induced by perturbations of the translational process as a shift in the frequency spectrum of extrinsic noise and a decrease in its weighting relative to intrinsic noise.

Animals↗
PubMed2003

The amplification of environmental noise in population models: causes and consequences.

Environmental variability is a ubiquitous feature of every organism's habitat. However, the interaction between density dependence and those density-independent factors that are manifested as environmental noise is poorly understood. We are interested in the conditions under which noise interacts with the density dependence to cause amplification of that noise when filtered by the system. For a broad family of structured population models, we show that amplification occurs near the threshold from stable to unstable dynamics by deriving an analytic formula for the amplification under weak noise. We confirm that the effect of noise is to sustain oscillations that would otherwise decay, and we show that it is the amplitude and not the phase that is affected. This is a feature noted in several recent studies. We study this phenomenon in detail for the lurchin and LPA models of population dynamics. We find that the degree of amplification is sensitive to both the noise input and life-history stage through which it acts, that the results hold for surprisingly high levels of noise, and that stochastic chaos (as measured by local Lyapunov exponents) is a concomitant feature of amplification. Further, it is shown that the temporal autocorrelation, or "color," of the noise has a major impact on the system response. We discuss the conditions under which color increases population variance and hence the risk of extinction, and we show that periodicity is sharpened when the color of the noise and dynamics coincide. Otherwise, there is interference, which shows how difficult it is in practice to separate the effects of nonlinearity and noise in short time series. The sensitivity of the population dynamics to noise when close to a bifurcation has wide-ranging consequences for the evolution and ecology of population dynamics.

Animals↗
PubMed1994

Noise and signal decoupling in maximum-likelihood reconstructions and Metz filters for PET brain images.

Images reconstructed with the maximum-likelihood-by-expectation-maximization (ML) algorithm have lower noise in some regions, particularly low count areas, compared with images reconstructed with filtered backprojection (FBP). The use of statistically correct noise model coupled with the positivity constraint in the ML algorithm provides this noise improvement, but whether this model confers a general advantage for ML over FBP with no noise model and any reconstruction filter, is unclear. We have studied the quantitative impact of the correct noise model in the ML algorithm applied to simulated and real PET fluoro-deoxyglucose (FDG) brain images, given a simplified but accurate reconstruction model with spatially invariant resolution. For FBP reconstruction, several Metz filters were chosen and images with different resolution were obtained depending on the order (1-400) of the Metz filters. Comparisons were made based on the mean Fourier spectra of the projection amplitudes, the noise-power spectra, and the mean region-of-interest signal and noise behaviour in the images. For images with resolution recovery beyond the intrinsic detector resolution, the noise increased significantly for FBP compared with ML. This indicates that in the process of signal recovery using ML, the noise is decoupled from the signal. Such noise decoupling is not possible for FBP. However, for image resolution equivalent to or less than the intrinsic detector resolution, FBP with Metz filters of various orders can achieve a performance similar to ML. The significance of the noise decoupling advantage in ML is dependent on the reconstructed image resolution required for specific imaging tasks.

Algorithms↗
PubMed2004

Noise equalization for detection of microcalcification clusters in direct digital mammogram images.

Equalizing image noise is shown to be an important step in the automatic detection of microcalcifications in digital mammography. This study extends a well established film-screen noise equalization scheme developed by Veldkamp et al. for application to full-field digital mammogram (FFDM) images. A simple noise model is determined based on the assumption that quantum noise is dominant in direct digital X-ray imaging. Estimation of the noise as a function of the gray level is improved by calculating the noise statistics using a truncated distribution method. Experimental support for the quantum noise assumption is presented for a set of step wedge phantom images. Performance of the noise equalization technique is also tested as a preprocessing stage to a microcalcification detection scheme. It is shown that the square root model based approach which FFDM allows leads to a robust estimation of the high frequency image noise. This provides better microcalcification detection performance when compared to the film-screen noise equalization method developed by Veldkamp. Substantially better results are obtained than when noise equalization is omitted. A database of 124 direct digital mammogram images containing 28 microcalcification clusters was used for evaluation of the method.

Algorithms↗
PubMed2003

New phase-noise model for crystal oscillators: application to the Clapp oscillator.

Leeson's is the basic model for predicting oscillator noise. A mathematical analysis of this "heuristic" model has been proposed. Both models do not detail the relative importance of the amplifier transfer function associated to its own noise with regard to that of the resonator. In this paper, an improved version of those previous models is presented. The phase noise generated by the amplifier and the one generated by the resonator are differentiated without considering their origins, such as the conversion of amplitude modulation noise into phase modulation noise. The power spectral densities of phase noise at various points of the oscillator loop are calculated from their respective correlation functions. As a consequence, the influence of the inner amplifier and resonator noises on the resulting oscillator noise is predictable. The model is especially attractive to the makers of widely used quartz oscillators. The resulting oscillator noise is easily obtained from the oscillator open-loop noise. An example of the phase-noise modeling of the Clapp quartz crystal oscillator is simulated and discussed.

Journal Article↗
PubMed2005

Subthreshold voltage noise of rat neocortical pyramidal neurones.

Neurones are noisy elements. Noise arises from both intrinsic and extrinsic sources, and manifests itself as fluctuations in the membrane potential. These fluctuations limit the accuracy of a neurone's output but have also been suggested to play a computational role. We present a detailed study of the amplitude and spectrum of voltage noise recorded at the soma of layer IV-V pyramidal neurones in slices taken from rat neocortex. The dependence of the noise on holding potential, synaptic activity and Na+ conductance is systematically analysed. We demonstrate that voltage noise increases non-linearly as the cell depolarizes (from a standard deviation (s.d.) of 0.19 mV at -75 mV to an s.d. of 0.54 mV at -55 mV). The increase in voltage noise is accompanied by an increase in the cell impedance, due to voltage dependence of Na+ conductance. The impedance increase accounts for the majority (70%) of the voltage noise increase. The increase in voltage noise and impedance is restricted to the low-frequency range (0.2-2 Hz). At the high frequency range (5-100 Hz) the voltage noise is dominated by synaptic activity. In our slice preparation, synaptic noise has little effect on the cell impedance. A minimal model reproduces qualitatively these data. Our results imply that ion channel noise contributes significantly to membrane voltage fluctuations at the subthreshold voltage range, and that Na+ conductance plays a key role in determining the amplitude of this noise by acting as a voltage-dependent amplifier of low-frequency transients.

Animals↗
PubMedDate not supplied

Effect of various noise sources on the detective quantum efficiency of phosphor screens.

We have examined the effect of screen-structure, optical-detector, and secondary-quantum noise sources on detective quantum efficiency, DQE(f). This was done by using experimental measurements of screen-structure and optical-detector noise in combination with a theoretical model which predicts x-ray quantum and secondary-quantum noise for different optical and physical properties of a phosphor screen. The reduction in DQE(f) from noise sources other than x-ray quantum noise depends on the noise power spectra (NPS) of these other sources relative to the x-ray quantum NPS. Even though x-ray quantum noise may be the dominant noise source at low spatial frequencies, it decreases relatively rapidly with increasing frequency so that other noise sources, which may be small at low frequencies, dominate. Our model predicts that DQE(f) can be increased, at spatial frequencies less than 4 mm-1, by changing the optical properties of the screen even though modulation transfer function MTF(f) may decrease. Furthermore, if screen and optical-detector noise decrease with increasing frequency and secondary-quantum noise sufficiently small, then DQE(f) will also be improved at frequencies greater than 4 mm-1.

Mathematics↗
PubMed2003

Recovery from prior stimulation: masking of speech by interrupted noise for younger and older adults with normal hearing.

In a previous study [Dubno et al, J. Acoust. Soc. Am. 111, 2897-2907 (2002)], older subjects benefitted less than younger subjects from momentary improvements in signal-to-noise ratio when listening to speech in interrupted maskers. It has been hypothesized that the benefit derived from interrupted maskers may be related to recovery from forward masking, i.e., the recovery of a response to a suprathreshold signal from prior stimulation by a masker. The effect of interrupted maskers on speech recognition may be well suited to test hypotheses regarding recovery from prior stimulation, given that both involve the perception of signals following a masker. Here, younger and older adults with normal but not identical audiograms listened to nonsense syllables at moderate and high levels in a speech-shaped noise that was modulated by a 2-, 10-, 25-, or 50-Hz square wave. An additional low-level noise was always present that was shaped to produce equivalent masked thresholds for all subjects. To assess recovery from forward masking, forward-masked thresholds were measured at 0.5 and 4.0 kHz as a function of the delay between the speech-shaped masker and the signal. Speech recognition in interrupted noise was poorer for older than younger subjects. Small but consistent age-related differences were observed in the decrease in score with interrupted noise relative to the score without interrupted noise. Forward-masked thresholds of older subjects were higher than those of younger subjects, but there were no age-related differences in the amount of forward masking or in simultaneous masking. Negative correlations were observed between speech-recognition scores in interrupted noise and forward-masked thresholds. That is, the benefit derived from momentary improvements in speech audibility in an interrupted noise decreased as forward-masked thresholds increased. Stronger correlations with forward masking were observed for the higher frequency signal, for higher noise interruption rates, and when the signal-to-noise ratio was poor. Comparisons of speech-recognition scores at moderate and high levels for younger and older subjects were not consistent with the hypothesis of an age-related difference in the contribution of low-spontaneous-rate fibers to speech recognition in interrupted noise.

Adult↗
PubMed1989

Noise susceptibility and immunity of phase locking in amphibian auditory-nerve fibers.

Recordings from auditory-nerve fibers in the anesthetized frog revealed that addition of broadband noise results in a reduction in the ability of a fiber to phase lock to a continuous pure tone. In particular, our results suggest that: (i) there is a threshold below which masking noise has little or no effect on vector strength (VS); then with increasing masking noise level, VS appears to decrease monotonically for all test frequencies (TFs); (ii) there exist subpopulations of auditory-nerve fibers in the frog for which the deterioration of phase locking to tones in wideband noise depends critically on the relationship of the TF to the fiber's CF. Specifically, in one subpopulation (43% of the fibers studied), the rate of VS decrease with increasing levels of masking noise is greater for CF tones than it is for TFs greater than CF. The net result is a "crossing" of the VS versus masking noise functions (e.g., Fig. 6); (iii) there exists a small subpopulation of amphibian papillar (a.p.) fibers for which the rate of VS decrease with increasing levels of masking noise is less for TFs less than CF than it is for CF tones (e.g., Fig. 5); (iv) there is a pronounced noise-induced phase lead for TFs greater than CF, whereas, for stimulus tones at or below CF, the preferred firing phase is nearly noise-level independent; (v) the remainder of the sample consists of fibers in which the VS-falloff rates appear to be test-frequency independent; (vi) addition of wideband masking noise to a CF tone, and increasing the CF-tone level in the absence of noise, produced (qualitatively) similar effects on the preferred firing phase of auditory-nerve fibers (e.g., Figs. 1 and 7). Thus amphibian auditory-nerve fibers appear to be energy detectors, i.e., exhibit phase shifts corresponding to the total energy within the filter passband defined by the frequency-threshold curve.

Animals↗
PubMed2001

Synaptic noise improves detection of subthreshold signals in hippocampal CA1 neurons.

Stochastic resonance (SR) is a phenomenon whereby the detection of a low-level signal is enhanced in a nonlinear system by the introduction of noise. Studies of the effects of SR in neurons have suggested that noise could play a prominent role in improving detection of small signals. Most experimental SR research has focused on the role of noise in sensory neurons using physiological stimuli. Computer simulations show that signal detection in hippocampal neurons is improved by the addition of physiological levels of noise applied extracellularly to synaptic inputs. These results were confirmed experimentally. We now report that endogenous noise sources can also improve signal detection. The noise source was generated by modulating the random synaptic activity on the apical dendrites of CA1 cells in rat hippocampal slices using subthreshold cathodic current. Intracellular recordings of CA1 cells showed that even small increases of synaptic noise are able to greatly improve the detection of an independent, synaptic, subthreshold stimulus as predicted by the simulations. The noise variance in the CA1 cell was compared with the resting variance and with variance changes caused by several endogenous noise sources. In all cases, the increased noise variance was well within the physiological range. These results were supplemented and analyzed with a CA1 computer model. The improved signal detection with small amounts of endogenous noise suggests that the diverse inputs to CA1 are able to improve detection of subthreshold synaptic signals and could provide a means to modulate detection of specific inputs in the hippocampus.

Action Potentials↗
PubMed2001

Noise reduction in oncology FDG PET images by iterative reconstruction: a quantitative assessment.

UNLABELLED: Tumor detection depends on the contrast between tumor activity and background activity and on the image noise in these 2 regions. The lower the image noise, the easier the tumor detection. Tumor activity contrast is determined by physiology. Noise, however, is affected by many factors, including the choice of reconstruction algorithm. Previous simulation and phantom measurements indicated that the ordered-subset expectation maximization (OSEM) algorithm may produce less noisy images than does the usual filtered backprojection (FBP) method, at equivalent resolution. To see if this prediction would hold in actual clinical situations, we quantified noise in clinical images reconstructed with both OSEM and FBP. METHODS: Three patients (2 with colon cancer, 1 with breast cancer) were imaged with FDG PET using a "gated replicate" technique that permitted accurate measurement of noise at each pixel. Each static image was acquired as a gated image sequence, using a pulse generator with a 1-s period, yielding 40 replicate images over the 10- to 15-min imaging time. The images were or were not precorrected for attenuation and were reconstructed with both FBP and OSEM at comparable resolution. From these data, images of pixel mean, SD, and signal-to-noise ratio (S/N) could be produced, reflecting only noise caused by the statistical fluctuations in the emission process. RESULTS: Noise did not vary greatly over each FBP image, even when image intensity varied greatly from one region to the next, causing S/N to be worse in low-activity regions than in high-activity regions. In contrast, OSEM had high noise in hot regions and low noise in cold regions. OSEM had a much better S/N than did FBP in cold regions of the image, such as the lungs (in the attenuation-corrected images), where improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in hotter areas such as the liver (averaging 25% improvement in the attenuation-corrected images). In very hot tumors, FBP actually produced higher S/Ns than did OSEM. CONCLUSION: We conclude that OSEM reconstruction can significantly reduce image noise, especially in relatively low-count regions. OSEM reconstruction failed to improve S/N in very hot tumors, in which S/N may already be adequate for tumor detection.

Algorithms↗
PubMed1998

The contribution of social noise to tinnitus in young people - a preliminary report.

In our study of the Hearing in Young Adults (HIYA) aged 18-25 years, there appeared to be little effect of social noise on hearing thresholds (Smith et al. 1998). There was however, a threefold increase in the reports of tinnitus in those subjects with significant social noise exposure (>/=97 dB NIL). No other abnormality was found of hearing function for those who were exposed to the most social noise. In an attempt to investigate this further we invited a sub-sample of those tested in the earlier phase of the study, to conduct further examinations of their hearing function. The three groups eventually consisted of those in the most social noise group who reported tinnitus (n=15) and those who did not (n=15), plus a group of people who had no social noise exposure but who reported tinnitus (n=8). All the groups were retested for their hearing thresholds, using standard audiometry and also the Audioscan technique to look for notches in the audiogram. Speech tests were carried out using an adaptive FAAF test. Transient-evoked oto-acoustic emissions were measured and also suppressed with a contralateral broad-band noise. Some evidence has been found to suggest that those young people who reported tinnitus are affected by social noise exposure, in terms of pure tone thresholds, speech tests, oto-acoustic emissions and reported hearing problems. Lessons can be drawn from our attempt to follow up this interesting population. First, the population is highly mobile and follow-up is difficult. Second, the presumed noise exposure was often not appropriate because even after a year it was possible for several individuals with insignificant social noise to move into the group with significant social noise exposure. Third, there is a need for a larger multi-centre study to look at the effect of social noise in more detail using a common protocol. The results of our study will be very useful in calculating the numbers needed in such a multi-centre study.

Journal Article↗
PubMed2000

A Review of Environmental Noise and Mental Health.

The question of whether environmental noise exposure causes mental ill-health is still largely unanswered. This paper reviews the studies of environmental and industrial noise and mental ill-health published between 1993 and 1998 and suggests possibilities for future research. Recent community based studies suggest high levels of environmental noise are associated with mental health symptoms such as depression and anxiety but not with impaired psychological functioning. Several studies find that self-reported noise sensitivity does not interact with noise exposure to lead to increased vulnerability to mental ill-health. Chronic aircraft noise exposure in children impairs quality of life but does not lead to depression or anxiety. Further research on environmental noise and mental health should be accompanied by more accurate and detailed measurement of noise exposure and consideration of the impact of other environmental stressors and careful measurement of confounding factors such as social class. Target study populations exposed to noise should be chosen to avoid those where noise exposure is likely to have led to noise sensitive individuals moving away from the area. There should also be greater use of standardised instruments to measure a wider range of mental health outcomes. Also other physiological outcomes such as hormonal measures could with benefit be measured simultaneously.

Journal Article↗
PubMed1999

Non-acoustical factors in noise management at Heathrow Airport.

Non-acoustic factors in environmental noise can be broadly defined as all those factors other than noise level alone which contribute to noise annoyance and similar effects. Noise levels such as LAeq provide a good indication of the amount of physical noise present, and changes in physical noise level can be expected to correlate with changes in resident's perception, at least to some degree. On the other hand, a flexible approach to noise management based on wide consultation and communication can be extremely important. At Heathrow Airport over the last 20 to 30 years, overall aircraft noise levels have reduced because of the phasing out of the older noisier Chapter 2 aircraft types, but there are also other strategies in place which are clearly regarded as being effective both by airport management and by local community representatives and which are not as easily quantified in terms of noise level alone. This paper describes the background to noise management at Heathrow in some detail and draws a general conclusion that taking non-acoustic factors into account in addition to physical noise levels alone has been of considerable benefit over the years.

Journal Article↗
PubMed2003

Impact of photon noise on the reliability of a motion-sensitive neuron in the fly's visual system.

Variable behavioral responses to identical visual stimuli can, in part, be traced back to variable neuronal signals that provide unreliable information about the outside world. This unreliability in encoding of visual information is caused by several noise sources such as photon noise, synaptic noise, or the stochastic nature of ion channels. Neurons of the fly's visual motion pathway have been claimed to represent perfect encoders, with photon noise as the main noise source limiting their performance. Other studies on the fly's visual system suggest, however, that internal noise emerging within the nervous system also affects the reliability of motion vision. To resolve these contradictory interpretations, we performed an electrophysiological investigation, inspired by the "equivalent noise" paradigm applied in psychophysics, on the fly's motion-sensitive H1 neuron. Noise-like brightness fluctuations of different strength were superimposed on the motion stimuli. Because the noise level found to affect the temporal properties of the spike responses is much larger than the estimate of photon noise under the experimental conditions, our results indicate that motion vision is more likely to be limited by internal sources of variability than by photon noise.

Action Potentials↗
PubMed1995

The signal-averaged ECG becomes late potential-positive at low noise levels in healthy subjects.

Late potentials are detected at various noise levels in clinical studies. The aim of this study was to quantify the effect of residual noise level on the signal-averaged ECG. Thirty minutes of raw ECG (lead -X, +X, -Y, +Y, -Z, and +Z) from 10 healthy volunteers were digitized and stored on optical discs. Each ECG was analysed by four signal averaging procedures to noise level 0.1, 0.2, 0.3, and 0.4 microV, respectively. At each noise level, time domain analysis of the filtered vector (40-250 Hz) included determination of the QRS duration (QRS), late potential duration (LPD, duration of terminal signals below 40 microV), and root-mean-square voltage of the terminal 40 ms of the filtered QRS (RMS40). On average, the measured signal-averaged QRS duration was prolonged by 7.0 ms (range 0.9-12.5 ms) per 0.1 microV reduction in noise level. Late potential duration increased by 5.9 ms (range 0.2-10.0 ms) per 0.1 microV reduction in noise level, and RMS40 was reduced by 9.1 microV (range 0.5-20.2 microV) per 0.1 microV reduction in noise level. At noise level 0.4 microV, 0.3 microV, 0.2 microV, and 0.1 microV the number of late potential-positive subjects were 1, 2, 4, and 6, respectively. Late potential parameters are significantly dependent on noise level after signal averaging. Using conventional criteria for late potentials, healthy subjects become false-positive at low noise levels. Establishment of standards for noise level is recommended.

Adult↗
PubMed2005

The global burden of occupational noise-induced hearing loss.

BACKGROUND: Excessive noise is a global occupational health hazard with considerable social and physiological impacts, including noise-induced hearing loss (NIHL). This paper describes the worldwide morbidity of occupational NIHL in the year 2000. METHODS: The proportion of the population exposed to occupational noise was estimated using noise exposure data from the US National Institute for Occupational Safety and Health (NIOSH), adjusted by data on the distribution of the work force by occupational category and economic sector, and economic activity rates in each WHO subregion. These values for the exposed population and risk measures for NIHL were used to develop estimates of the attributable fraction (AF) of adult-onset hearing loss resulting from occupational noise exposure. The AFs were applied to WHO estimates of total disability-adjusted life years (DALYs) from adult-onset hearing loss to estimate the DALYs due to occupational noise. RESULTS: Worldwide, 16% of the disabling hearing loss in adults (over 4 million DALYs) is attributed to occupational noise, ranging from 7% to 21% in the various subregions. The effects of the exposure to occupational noise are larger for males than females in all subregions and higher in the developing regions. CONCLUSIONS: Occupational noise is a significant cause of adult-onset hearing loss. The majority of this NIHL burden can be minimized by the use of engineering controls to reduce the generation of noise at its source.

Adolescent↗
PubMed1984

Single and joint actions of noise and sinusoidal whole body vibration on TTS2 values and low frequency upright posture sway in men.

In the present study the changes in the TTS2 values and body upright posture sway were examined after exposure of subjects (n = 10) to stable broadband (white) noise (90 dB) alone, to sinusoidal vibration alone [directed vertically at the whole body (Z axis)], and to simultaneous exposure combinations of noise and vibrations of the same type. The frequency of the vibration was 5 Hz, but its acceleration was either 2.12 or 2.44 m/s2. There were six exposure combinations, and subsequently 60 tests were carried out in an exposure chamber. One test consisted of a control period of 30 min, of three consecutive exposure periods of 16 min each and of a recovery period of 15 min. After the three exposure combinations which included noise, half of the subjects were exposed to vibration during the recovery period. Apart from indicating an increase in the temporary hearing threshold, the results showed that simultaneous exposure to noise and vibration increases the instability of the body upright posture. The TTS2 values at the 4 and 6 kHz frequencies increased considerably more rapidly when the subjects were exposed simultaneously to noise and vibration than when exposed to noise alone. Without exception, the TTS2 values increased most during the first exposure period. It was noteworthy that exposure to vibration during the recovery period accelerated the recursion of the TTS2 values, especially in cases where the subjects had been exposed to noise alone. The variance of the body sway amplitudes and the standard deviation increased within the frequency range 0.063-2.000 Hz owing to noise alone and simultaneous noise and vibration. In the directions X and Y, within the frequency ranges 0.063-0.100 Hz and 0.100-0.600 Hz, the means of the maximum amplitudes of body sway increased especially in connection with those tests in which the subjects had been simultaneously exposed to noise and vibration.

Adult↗