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Biomedical subjects

L R Bernstein

Publications and source records attributed to L R Bernstein.

At least 19 recordsLinked to original sources
PubMed2001

Auditory processing of interaural timing information: new insights.

Differences in the time-of-arrival of sounds at the two ears, or interaural temporal disparities (ITDs), constitute one of the major binaural cues that underlie our ability to localize sounds in space. In addition, ITDs contribute to our ability to detect and to discriminate sounds, such as speech, in noisy environments. For low-frequency signals, ITDs are conveyed primarily by "cycle-by-cycle" disparities present in the fine-structure of the waveform. For high-frequency signals, ITDs are conveyed by disparities within the time-varying amplitude, or envelope, of the waveform. The results of laboratory studies conducted over the past few decades indicate that ITDs within the envelopes of high-frequency are less potent than those within the fine-structure of low-frequency stimuli. This is true for both measures of sensitivity to changes in ITD and for measures of the extent of the perceived lateral displacement of sounds containing ITDs. Colburn and Esquissaud (1976) hypothesized that it is differences in the specific aspects of the waveform that are coded neurally within each monaural (single ear) channel that account for the greater potency of ITDs at low frequencies rather than any differences in the more central binaural mechanisms that serve these different frequency regions. In this review, the results of new studies are reported that employed special high-frequency "transposed" stimuli that were designed to provide the high-frequency channels of the binaural processor with envelope-based information that mimics waveform-based information normally available only in low-frequency channels. The results demonstrate that these high-frequency transposed stimuli (1) yield sensitivity to ITDs that approaches, or is equivalent to, that obtained with "conventional" low-frequency stimuli and (2) yield large extents of laterality that are similar to those measured with conventional low-frequency stimuli. These findings suggest that by providing the high-frequency channels of the binaural processor with information that mimics that normally available only at low frequencies, the potency of ITDs in the two frequency regions can be made to be similar, if not identical. These outcomes provide strong support for Colburn and Esquissaud's (1976) hypothesis. The use of high-frequency transposed stimuli, in both behavioral and physiological investigations offers the promise of new and important insights into the nature of binaural processing.

Acoustic Stimulation↗
PubMed2001

A new analytical scale DNA affinity binding assay for analyses of specific protein-DNA interactions.

We describe a rapid analytical assay for identification of proteins binding to specific DNA sequences. The DAPSTER assay (DNA affinity preincubation specificity test of recognition assay) is a DNA affinity chromatography-based microassay that can discriminate between specific and nonspecific protein-DNA interactions. The assay is sensitive and can detect protein-DNA interactions and larger multicomponent complexes that can be missed by other analytical methods. Here we describe in detail the optimization and utilization of the DAPSTER assay to isolate AP-1 complexes and associated proteins in multimeric complexes bound to the AP-1 DNA element.

Binding Sites↗
PubMed2001

Ten ERK-related proteins in three distinct classes associate with AP-1 proteins and/or AP-1 DNA.

We have identified seven ERK-related proteins ("ERPs"), including ERK2, that are stably associated in vivo with AP-1 dimers composed of diverse Jun and Fos family proteins. These complexes have kinase activity. We designate them as "class I ERPs." We originally hypothesized that these ERPs associate with DNA along with AP-1 proteins. We devised a DNA affinity chromatography-based analytical assay for DNA binding, the "nucleotide affinity preincubation specificity test recognition" (NAPSTER) assay. In this assay, class I ERPs do not associate with AP-1 DNA. However, several new "class II" ERPs do associate with DNA. p41 and p44 are ERK1/2-related ERPs that lack kinase activity and associate along with AP-1 proteins with AP-1 DNA. Class I ERPs and their associated kinase activity thus appear to bind AP-1 dimers when they are not bound to DNA and then disengage and are replaced by class II ERPs to form higher order complexes when AP-1 dimers bind DNA. p97 is a class III ERP, related to ERK3, that associates with AP-1 DNA without AP-1 proteins. With the exception of ERK2, none of the 10 ERPs appear to be known mitogen-activated protein kinase superfamily members.

Binding Sites↗
PubMed2001

Manipulating the "straightness" and "curvature" of patterns of interaural cross correlation affects listeners' sensitivity to changes in interaural delay.

The purpose of this study was to test the hypothesis that stimuli characterized by "straight" trajectories of their patterns of cross correlation foster greater sensitivity to changes in interaural temporal disparities (ITDs) than do stimuli characterized by more "curved" trajectories of their patterns of cross correlation. To do so, sensitivity to changes in ITD was measured, as a function of duration, using a set of "reference" stimuli that yielded differing relative amounts of straightness within their patterns of cross correlation while keeping the dominant trajectory at or near midline. The relative amounts of straightness were manipulated by employing specific combinations of bandwidth, ITD, and interaural phase disparity (IPD) of Gaussian noises centered at 500 Hz. The results were consistent with expectations in that the patterning of the threshold ITDs revealed increasingly poorer sensitivity as greater and greater curvature was imposed on the dominant, "midline," trajectory. The variations in threshold ITD across the stimulus conditions can be accounted for quite well quantitatively by assuming either that the listeners based their judgments on changes in the position of the most central peak of the cross-correlation function or that they based their judgments on changes in the centroid of a second-level cross-correlation function. In a second experiment, binaural detection was measured using a subset of the reference stimuli as maskers. As expected, sensitivity was poorest with the maskers characterized by the greatest curvature, which were also those having the lowest interaural correlation.

Adult↗
PubMed2001

A consideration of the normalization that is typically included in correlation-based models of binaural detection.

An analysis of binaural detection and new data that elucidate the nature and precision of normalization that must be assumed if binaural detection is accomplished via mechanisms that effectively compute the coefficient of cross correlation is presented. Based on that analysis, it is argued that the precision of normalization required to remove deleterious effects resulting from variations in the levels of the stimuli is so great that it is highly unlikely that normalization, per se, actually occurs as part of binarual processing. Instead, it appears more likely that binaural processing is accomplished via "subtractive" mechanisms, such as the one originally described by Durlach [J. Acoust. Soc. Am. 35, 1206-1218 (1963)]. Within that framework, deleterious effects that could result from variations in the levels of the stimuli simply do not arise.

Auditory Perception↗
PubMed2001

Sensitivity to brief changes of interaural time and interaural intensity.

The purpose of this study was to measure listeners' abilities to detect brief changes in interaural temporal disparities (ITDs) or interaural intensitive disparities (IIDs) conveyed by bursts of noise (probes) temporally and symmetrically flanked by segments of diotic or uncorrelated noise. Thresholds were measured using a four-interval, two-alternative, forced-choice adaptive task and the total duration of the bursts of noise was either 20, 40, or 100 ms. Probes were temporally centered within each burst and the durations of the probes ranged from 2 to 100 ms, depending upon the duration of the (longer) total burst of noise within which they were embedded. The results indicate that, for a given total duration of noise, there is a rapid decrease in threshold ITD or threshold IID as the duration of the probe is increased so that it occupies a larger portion of the total burst of noise. Mathematical analyses revealed that both threshold ITDs and threshold IIDs could be well accounted for by assuming that the listener processes both types of binaural cues via a single, symmetric, double-exponential temporal window. Interestingly, the shapes of the temporal windows that fit the data obtained from the human listeners resemble the shapes of the temporal windows derived by Wagner [H. Wagner, J. Comp. Physiol. A 169, 281-289 (1991)], who studied the barn owl. The time constants and relative weightings yielded temporal window functions that heavily emphasize information occurring within the very temporal center of the window. This temporal window function was found to be generalizable in the sense that it also accounts for classic data reported by Grantham and Wightman [D.W. Gratham and F.L. Wightman, J. Acoust. Soc. Am. 63, 511-523 (1978)] concerning sensitivity to dynamically changing interaural disparities.

Acoustic Stimulation↗
PubMed2001

The variation across time of sensitivity to interaural disparities: behavioral measurements and quantitative analyses.

Zurek (1980) measured listeners' sensitivities to interaural disparities conveyed by a 5-ms "probe" segment embedded within a 50-ms burst of otherwise diotic broadband noise [P. M. Zurek, J. Acoust. Soc. Am. 67, 952-964 (1980)]. He found that thresholds for interaural time delay (ITD) and interaural intensitive difference (IID) were markedly elevated when the onset of the probe segment occurred between 1 and 5 ms after the onset of the burst. Zurek postulated that this occurred because the leading portion of the noise briefly inhibited sensitivity to subsequent binaural information. If such inhibition were the primary factor responsible for the elevation in thresholds, then the omission of the portion of the noise trailing the probe segment would be expected to have little, if any, influence on performance. In order to test this hypothesis, listeners' sensitivities to ITD and IID were measured using a paradigm similar to that employed by Zurek. The results revealed that the omission of either the leading or the trailing portions of the diotic noise led to substantial reductions in threshold ITDs and IIDs. The data were successfully accounted for by a model based upon a combination of a temporal window with an equivalent rectangular duration of approximately 10 ms and a weighting function representing a brief loss of binaural sensitivity just after the onset of a sound.

Adult↗
PubMed1999

Tumor promotion resistant cells are deficient in AP-1 DNA binding, JunD DNA binding and JunD expression and form different AP-1-DNA complexes than promotion sensitive cells.

The JB6 cell culture model is used to identify molecular determinants of susceptibility to the promotion of neoplastic transformation. Clonal variants susceptible to transformation ('P+' cells) form numerous anchorage-independent colonies in soft agar upon treatment with the phorbol ester tumor promoter TPA, whereas resistant variants ('P-' cells) do not. We now report that there is significantly less binding of activator protein-1 (AP-1) to its DNA binding site in P- cells than in P+ cells. Gel supershift assays were performed to detect association of all seven AP-1 family members with their DNA binding site in TPA-treated and -untreated P+ and P- cells. Significantly lower DNA binding and protein expression of JunD were detected in P- cells than in P+ cells. c-Jun was detected in P+, but not P-, AP-1-DNA complexes, and c-Fos was detected in P-, but not P+, AP-1-DNA complexes. These and other phenotype-specific differences in abundance and composition of AP-1-DNA complexes may play a role in the resistance of P- cells to tumor promoter-induced transformation.

Base Sequence↗
PubMed1999

The effects of signal duration on NoSo and NoS pi thresholds at 500 Hz and 4 kHz.

A two-interval, two-alternative temporal forced-choice procedure was used to measure NoSo and NoS pi masked thresholds with 500-Hz and 4-kHz tonal signals. The duration of the signal was either 10, 20, 40, or 320 ms. The maskers were 200-Hz-wide bands of Gaussian noise centered at the frequency of the signal and presented continuously. Decreasing the duration of the 500-Hz tonal signal resulted in a modest increase (1.5 dB or so) in the masking-level difference (MLD) measured between NoSo and NoS pi conditions. In contrast, decreasing the duration of the 4-kHz tonal signal resulted in a substantial decrease (4.5 dB or so) in the MLD. Comparisons of the data with thresholds predicted from analyses based on "windows of temporal integration" provided quantitatively acceptable accounts of the data. The data obtained in the NoS pi condition at 4 kHz, which are novel and were of primary interest, were well-accounted for in a statistical sense. However, there were small, but systematic, discrepancies between the predictions and the data. Those discrepancies, although small in magnitude, suggest that binaural temporal integration at high frequencies, where the envelopes of the stimuli convey the information, may be inherently different from both monaural temporal integration and binaural temporal integration at low frequencies.

Auditory Perception↗
PubMed1999

The normalized interaural correlation: accounting for NoS pi thresholds obtained with Gaussian and "low-noise" masking noise.

Recently, Eddins and Barber [J. Acoust. Soc. Am. 103, 2578-2589 (1998)] and Hall et al. [J. Acoust. Soc. Am. 103, 2573-2577 (1998)] independently reported that greater masking of interaurally phase-reversed (S pi) tones was produced by diotic low-noise noise than by diotic Gaussian noise. Based on quantitative analyses, Eddins and Barber suggested that their results could not be accounted for by assuming that listeners' judgments were based on constant-criterion changes in the normalized interaural correlation produced by adding the S pi signal to the diotic masker. In particular, they showed that a model like the one previously employed by Bernstein and Trahiotis [J. Acoust. Soc. Am. 100, 3774-3784 (1996)] predicted an ordering of thresholds between the conditions of interest that was opposite to that observed. Bernstein and Trahiotis computed the normalized interaural correlation subsequent to half-wave, square-law rectification and low-pass filtering, the parameters of which were chosen to mimic peripheral auditory processing. In this report, it is demonstrated that augmenting the model by adding a physiologically valid stage of "envelope compression" prior to rectification and low-pass filtering provides a remedy. The new model not only accounts for the data obtained by Eddins and Barber (and the similar data obtained by Hall et al.), but also does not diminish the highly successful account of the comprehensive set of data that gave rise to the original form of the model. Therefore, models based on the computation of the normalized interaural correlation appear to remain valid because they can account, both quantitatively and qualitatively, for a wide variety of binaural detection and discrimination data.

Auditory Perception↗
PubMed1998

Inter-individual differences in binaural detection of low-frequency or high-frequency tonal signals masked by narrow-band or broadband noise.

Detection thresholds for either 500-Hz tones or 4-kHz tones were measured for a group of 19 listeners utilizing the interaural configurations NoSo and NoS pi. Both broadband (100-8500 Hz) noises and narrow-band (50-Hz-wide) noises served as maskers. In addition, direct measures of the listeners' sensitivities to changes in interaural temporal differences (ITDs) and interaural intensitive differences (IIDs) were measured using 400-Hz-wide noises centered at 500 Hz or 4 kHz. A rather large range of inter-individual differences in threshold was observed for 4-kHz tonal signals masked by narrow-band noise in the NoS pi configuration. This result is consistent with several sets of data from our previous experiments conducted over more than a decade. A broad range of thresholds was also obtained for 500-Hz tonal signals masked by narrow-band noise in the NoS pi configuration. This outcome, coupled with the fact that the use of a broadband masker did not yield a large distribution of thresholds for the detection of a 500-Hz tone masked by a broad band of noise, suggests that it is the use of a narrow-band masker, per se, that results in a large range of thresholds. Statistical analyses revealed that thresholds in the NoS pi detection tasks were not highly correlated with thresholds measured in the ITD- and the IID-discrimination tasks. Nevertheless, the five listeners who were the most sensitive in the narrow-band NoS pi detection and the five listeners who were the least sensitive in the narrow-band NoS pi detection tasks were those who were the most and least sensitive, respectively, to changes in ITDs and to changes in IIDs.

Auditory Perception↗
PubMed1997

The effects of randomizing values of interaural disparities on binaural detection and on discrimination of interaural correlation.

The purpose of this study was to assess whether randomizing (roving) baseline interaural parameters of binaural stimuli would adversely affect performance in masking-level differences and in interaural correlation-discrimination paradigms. Listeners' detection thresholds were measured in NoSo and NoS pi configurations for both broadband (100-3000 Hz) and narrow-band (450-550 Hz) maskers centered at 500 Hz. In addition, thresholds of interaural decorrelation (from a reference correlation of 1.0) were measured for 100-Hz-wide bands of noise centered at 500 Hz. Data were obtained under conditions in which either values of ITD or values of IID were roved both within and across trials. Data were also collected in the absence of a rove. The range of the rove was +/- 500 microseconds for ITDs and was +/- 6 dB for IIDs. The duration of the stimuli was varied between 17 and 310 ms. Overall, the results indicate that, independent of duration, roving the interaural cues produced small degradations of performance as compared to data obtained in the absence of a rove. The data are inconsistent with the notion that binaural detection depends upon reliable changes in laterality produced by adding S pi signals to diotic maskers. On the other hand, the data are consistent with modern models of binaural processing.

Auditory Perception↗
PubMed1996

On the use of the normalized correlation as an index of interaural envelope correlation.

The purpose of the present study was to obtain new empirical observations that would help determine the form of interaural envelope correlation that accounts for listeners' sensitivity to binaural information conveyed by high-frequency stimuli. In a four-interval, two alternative task, listeners detected which interval contained a 4-kHz tone added antiphasically to diotic, 200-Hz-wide noise (NoS pi). The "nonsignal" intervals contained the tone added homophasically (NoSo). Discriminability (d') was measured as a function of S/N for values between -30 and +30 dB. For all S/Ns, overall level was 70 dB SPL. Using a similar procedure, listeners were also tested in "direct" discrimination tasks where changes in envelope correlations were produced in one of two manners. First, changes in the normalized interaural envelope correlation were produced by varying the degree to which the envelopes covaried. This was accomplished by "mixing" two independent Gaussian noises. Second, changes in the normalized interaural envelope correlation were produced by adding dc values to the envelopes of the stimuli. Overall, in both experiments, listeners' ability to discriminate changes in interaural envelope correlation (from a base correlation of 1.0) was well accounted for by the normalized correlation. It is also shown that the normalized correlation of the envelope accounts for classic data concerning discriminability of interaural time differences at high frequencies as a function of depth of modulation.

Auditory Perception↗
PubMed1996

The normalized correlation: accounting for binaural detection across center frequency.

Bernstein and Trahiotis [L. R. Bernstein and C. Trahiotis, J. Acoust. Soc. Am. 100, 1754-1763 (1996)] recently reported the results of experiments designed to determine the form of interaural correlation that accounts for listeners' sensitivities to interaural disparities within high-frequency stimuli. Overall, those results demonstrated that listeners' abilities to discriminate changes in the interaural correlation of the envelope (from a base correlation of 1.0) were well accounted for by the use of the normalized correlation. The purpose of this study was to determine how well the normalized correlation computed subsequent to half-wave rectification and low-pass filtering could account for binaural detection data at low, intermediate, and high frequencies, respectively. In a four-interval, two-alternative task, listeners detected which interval contained a tone (between 500 Hz and 2 kHz) added antiphasically to diotic, 100-Hz-wide, noise (NoS pi). "Nonsignal" intervals contained the tone added homophasically (NoSo). Performance was measured for signal-to-noise ratios between -30 and +30 dB. Results indicated that a low-pass filter function based on physiological measures of synchrony in cochlear nerve fibers in conjunction with the assumption of half-wave, square-law rectification, accounted for typically 80% of the variance in the behavioral data.

Humans↗
PubMed1995

c-jun and multistage carcinogenesis: association of overexpression of introduced c-jun with progression toward a neoplastic endpoint in mouse JB6 cells sensitive to tumor promoter-induced transformation.

Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) induce neoplastic transformation, elevated c-jun protein expression, and activator protein-1 (AP-1)-dependent gene expression in JB6 mouse epidermal cells sensitive to tumor promoters (clone 415a P+ cells). In contrast, JB6 cells resistant to tumor promoter-induced transformation (clone 307b P- cells) exhibit a greatly reduced TPA or EGF inducible c-jun expression and AP-1 activity. We have recently shown that induced AP-1 is necessary for tumor promoter-induced transformation of P+ cells because introduction of a dominant negative c-jun mutant into P+ cells inhibits both AP-1 dependent transactivation and the transformation response to tumor promoter. The intent of the investigation presented here was to test the hypothesis that elevation of AP-1 activity is sufficient to cause progression to the P+ phenotype in P- cells or to the transformed phenotype in P+ cells. Clonally derived P+ and P- recipient cells transfected with a human c-jun expression construct and overexpressing c-jun protein were tested for progression by assaying for constitutive or inducible anchorage independent phenotype and nude-mouse tumorigenicity. Overexpression of c-jun did not produce progression in P- cells but did increase the probability of progression in P+ cells (two of five transfectant cell lines progressed to the tumor phenotype). In addition, c-jun overexpression did not increase AP-1 activity in any of the P-/c-jun transfectants or in the two of five P+/c-jun transfectants that acquired the transformed phenotype. The P+/c-jun transfectants that showed elevated AP-1 activity did not progress to the tumor phenotype, demonstrating that an increase in AP-1 activity is insufficient for this progression. Since P(+)-to-tumor phenotype progression occurred in cells overexpressing c-jun but not AP-1, we propose that P(+)-to-transformed phenotype progression is c-jun dependent and AP-1 independent.

Animals↗
PubMed1995

Binaural interference effects measured with masking-level difference and with ITD- and IID-discrimination paradigms.

The results of several studies have demonstrated that the ability to process binaural information within discrete spectral regions may be degraded by the presence of information at other, even remote, spectral loci. This study focused on binaural interference produced by low-frequency noises (centered at 500 Hz) on the processing of interaural disparities within high-frequency bands of noise (centered on 4 kHz). The bandwidths of the interferers and "targets" were either the same (either 100 or 400 Hz) or different (interferer: 100 Hz; target: 400 Hz). Within a single group of listeners, interference was measured with a masking-level difference paradigm (NoSo vs NoS pi), and in ITD- and IID-discrimination tasks. An important feature of the experiments was the utilization, parametrically, in all three tasks, of pulsed and continuous interferers that were either diotic or were interaurally uncorrelated. As reported in previous experiments, the amounts of interference obtained with pulsed interferers were much greater than those obtained with continuous interferers. The present experiment extends that general finding to discrimination of IIDs. In addition, in all three tasks, pulsed, interaurally uncorrelated interferers produced greater amounts of interference than did pulsed, diotic interferers. The patterns of interference effects found across bandwidths and listeners for the four interference conditions (pulsed-diotic, continuous-diotic, pulsed-uncorrelated, and continuous-uncorrelated) in the MLD paradigm were different than those obtained in either the ITD- or IID-discrimination tasks. One factor that may account for the diverging patterns of interference is that the interaural cues produced by adding the S pi signal to the diotic masker fluctuated in magnitude over time. In contrast, the ITDs and IIDs in the discrimination task were static.(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory Threshold↗