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Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism.

ABSTRACT: Chemical gradients can generate pattern formation in biological systems. In the fission yeast Schizosaccharomyces pombe, a cortical gradient of pom1p (a DYRK-type protein kinase) functions to position sites of cytokinesis and cell polarity and to control cell length. Here, using quantitative imaging, fluorescence correlation spectroscopy, and mathematical modeling, we study how its gradient distribution is formed. Pom1p gradients exhibit large cell-to-cell variability, as well as dynamic fluctuations in each individual gradient. Our data lead to a two-state model for gradient formation in which pom1p molecules associate with the plasma membrane at cell tips and then diffuse on the membrane while aggregating into and fragmenting from clusters, before disassociating from the membrane. In contrast to a classical one-component gradient, this two-state gradient buffers against cell-to-cell variations in protein concentration. This buffering mechanism, together with time averaging to reduce intrinsic noise, allows the pom1p gradient to specify positional information in a robust manner.

SUBMITTER: Saunders TE

PROVIDER: S-EPMC3312004 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism.

Saunders Timothy E TE Pan Kally Z KZ Angel Andrew A Guan Yinghua Y Shah Jagesh V JV Howard Martin M Chang Fred F

Developmental cell 20120216 3

Chemical gradients can generate pattern formation in biological systems. In the fission yeast Schizosaccharomyces pombe, a cortical gradient of pom1p (a DYRK-type protein kinase) functions to position sites of cytokinesis and cell polarity and to control cell length. Here, using quantitative imaging, fluorescence correlation spectroscopy, and mathematical modeling, we study how its gradient distribution is formed. Pom1p gradients exhibit large cell-to-cell variability, as well as dynamic fluctua ...[more]

PMID: 22342545

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Project description:ObjectivesHearing aid processing in realistic listening environments is difficult to study effectively. Often the environment is unpredictable or unknown, such as in wearable aid trials with subjective report by the wearer. Some laboratory experiments create listening environments to exert tight experimental control, but those environments are often limited by physical space, a small number of sound sources, or room absorptive properties. Simulation techniques bridge this gap by providing greater experimental control over listening environments, effectively bringing aspects of the real-world into the laboratory. This project used simulation to study the effects of wide-dynamic range compression (WDRC) and digital noise reduction (DNR) on speech intelligibility in a reverberant environment with six spatialized competing talkers. The primary objective of this study was to determine the efficacy of WDRC and DNR in a complex listening environment using virtual auditory space techniques.DesignParticipants of greatest interest were listeners with hearing impairment. A group of listeners with clinically normal hearing was included to assess the effects of the simulation absent the complex effects of hearing loss. Virtual auditory space techniques were used to simulate a small restaurant listening environment with two different reverberation times (0.8 and 1.8 sec) in a range of signal to noise ratios (SNRs) (-8.5 to 11.5 dB SNR). Six spatialized competing talkers were included to further enhance realism. A hearing aid simulation was used to examine the degree to which speech intelligibility was affected by slow and fast WDRC in conjunction with the presence or absence of DNR. The WDRC and DNR settings were chosen to be reasonable estimates of hearing aids currently available to consumers.ResultsA WDRC × DNR × Hearing Status interaction was observed, such that DNR was beneficial for speech intelligibility when combined with fast WDRC speeds, but DNR was detrimental to speech intelligibility when WDRC speeds were slow. The pattern of the WDRC × DNR interaction was observed for both listener groups. Significant main effects of reverberation time and SNR were observed, indicating better performance with lower reverberation times and more positive SNR.ConclusionsDNR reduced low-amplitude noise before WDRC-amplified the low-intensity portions of the signal, negating one potential downside of fast WDRC and leading to an improvement in speech intelligibility in this simulation. These data suggest that, in some real-world environments that include both reverberation and noise, older listeners with hearing impairment may find speech to be more intelligible if DNR is activated when the hearing aid has fast compression time constants. Additional research is needed to determine the appropriate DNR strength and to confirm results in wearable hearing aids and a wider range of listening environments.

Project description:PurposeMost modern hearing aids (HAs) employ wide dynamic range compression (WDRC) and noise reduction (NR) algorithms. It is known that the nonlinear effects of WDRC and NR cause changes to the output signal-to-noise ratio (SNR) of an HA. However, the relative contributions of WDRC and NR to the nonlinear effects are not fully understood. The current study investigated (a) whether WDRC or NR dominates the nonlinear effects measured at the output of a digital HA and (b) whether the electroacoustic effectiveness of NR depends on WDRC parameters while input SNR and background noise are systematically varied.MethodTest stimuli were Connected Speech Test sentences in multitalker babble noise (2- or 20-talker), presented at input SNRs ranging from -10 to +10 dB. The HA was programmed using multiband WDRC set according to the National Acoustic Laboratories for Nonlinear HA fitting formula 2 prescriptive fits for four standard audiograms and two compression speeds. The NR algorithm of the HA was switched on or off in separate conditions. Nonlinear electroacoustic effects from the WDRC and NR algorithms were assessed by measuring the output SNR of the HA using a phase-inversion technique. To investigate whether there are other factors that may be important besides the output SNR, the Hearing Aid Speech Intelligibility Index and the Hearing Aid Speech Quality Index were applied to the recordings to generate inferences on aided speech intelligibility and perceived speech quality.ResultsResults showed that WDRC dominated the net nonlinear effect at low-input SNRs, and the net nonlinear effect of WDRC and NR was reduced at high-input SNRs. Results also showed that the effectiveness of NR depended on compression parameters. The effectiveness of NR was partially explained by the trend of Hearing Aid Speech Intelligibility Index and Hearing Aid Speech Quality Index scores, potentially indicating that the Hearing Aid Speech Intelligibility Index and Hearing Aid Speech Quality Index scores may capture factors that cannot be captured by the output SNR metric.ConclusionsResults suggest that the individual signal-processing stages in an HA should not be considered as independent. Electroacoustic evaluation of WDRC and NR algorithms in isolation is not sufficient to capture the combined nonlinear effect of the two algorithms.Supplemental materialhttps://doi.org/10.23641/asha.25962541.

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Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism.

Publications

Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism.

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