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L R Bernstein

Publications and source records attributed to L R Bernstein.

At least 37 records · Page 2Linked to original sources

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↗

A family of mitogen-activated protein kinase-related proteins interacts in vivo with activator protein-1 transcription factor.

The activator protein-1 (AP-1) transcription factor modulates expression of genes involved in growth regulation, differentiation, and neoplastic transformation. Several mitogen-activated protein kinases (MAP kinases) as well as other kinases phosphorylate c-Jun and c-Fos in vitro and are postulated to control AP-1 activity. However, since many protein kinases phosphorylate substrates in vitro with which they have no association in vivo, we sought evidence for interaction in vivo between AP-1 and MAP kinase proteins. We now report detection of an association in vivo of MAP kinase-related proteins with c-Jun and AP-1 dimers by peptide mapping and two-dimensional electrophoretic analyses of proteins co-immunoprecipitated with AP-1 antigens. Extracellular signal-regulated kinase-2 and several apparently novel MAP kinase-related proteins are among the species that bind to AP-1. The large number of MAP kinase-related proteins associated with AP-1 implicates them on an important gene regulation pathway. Combinatorial association between MAP kinase-related proteins and AP-1 dimers could potentially create numerous distinct complexes that could regulate diverse genes.

Animals↗

Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis.

Metastasis and tumor angiogenesis are invasive phenomena and share many common properties at the physiological level and some similarities at the molecular level. Each consists of repetitive cycles of interaction with adjacent extracellular matrix components by mediating cellular adhesion, matrix dissolution, and cellular motility to achieve metastasis of cancer cells or neovascularization of tumors. Molecular factors which implement this triad of events are reviewed, as are several signal transduction components which may regulate them. Some potentially promising prognostic, diagnostic, and therapeutic modalities for tumor angiogenesis and metastatic disease are also discussed.

Cell Adhesion↗

The effect of nonsimultaneous on-frequency and off-frequency cues on the detection of a tonal signal masked by narrow-band noise.

Listeners' detection thresholds were measured for a 125-ms, 1-kHz tonal signal masked by a similarly gated 50-Hz-wide band of noise. A two-interval, adaptive, forced-choice procedure either with or without temporally surrounding cuing intervals containing 50-Hz-wide bands of noise was employed. When the cues were present, their center frequency was either 1 kHz (on-frequency) or 900 or 700 Hz (off-frequency). In the conditions of principal interest, the envelopes and phase modulations of the bands of noise were "frozen" across the four intervals that defined a trial, but were chosen randomly across trials. Thresholds were lowest with cues centered at 1 kHz and increased substantially when the center frequency of the cues was changed to 900 or 700 Hz. With cues centered at 700 Hz, performance was equivalent to that obtained without cues and with the masking noise "frozen" across the two intervals that defined a trial. A similar pattern of results was obtained with high-frequency stimuli, where sensitivity to fine-structure information is greatly reduced. Roving the level of the stimuli over a 40-dB range generally reduced sensitivity but did not greatly affect the overall pattern of the data. Thresholds obtained in the two-interval task with masking waveforms chosen randomly were compared with thresholds obtained when the masking waveform was "frozen" within, but not across trials. Differences in threshold appeared to be accounted for by the listeners' use of changes in the mean slope of the envelope of the noise produced by adding the tonal signal.

Acoustic Stimulation↗

Detection of interaural delay in high-frequency sinusoidally amplitude-modulated tones, two-tone complexes, and bands of noise.

Listeners' ability to detect interaural temporal disparities (ITDs) was investigated for 160-ms, sinusoidally amplitude modulated (SAM) tones, two-tone complexes, and bands of noise at center frequencies of 4, 8, or 12 kHz. Rates of modulation for the 100%-modulated SAM tones and frequency separation for the equal-amplitude, two-tone complexes ranged from 32-768 Hz, depending on center frequency. Noise bandwidths ranged from 50-2000 Hz, also depending on center frequency. The data indicate, consistent with previous results, that sensitivity to ITD with the SAM and two-tone complexes decreases as the rate of envelope fluctuation increases beyond about 400 Hz. The decline in performance is not due simply to reduced depths of modulation produced by critical-band-like filtering, but is consistent with an inability to "follow" or encode high rates of modulation. For bands of noise, sensitivity to ITD was relatively constant as a function of bandwidth. Generally, sensitivity to ITD decreased as center frequency was increased from 4 to 8 kHz, but the relations among the data were essentially unchanged. Increasing the center frequency to 12 kHz resulted in very poor performance.

Acoustic Stimulation↗

Spectral interference in a binaural detection task: effects of masker bandwidth and temporal fringe.

Recently, it was reported that the detectability of a 100-ms, 800-Hz tone (the target) presented antiphasically (S pi) against a background of continuous, broadband, diotic noise could be degraded if a 400-Hz tone (the interferer) was gated simultaneously with the target [L. R. Bernstein, J. Acoust. Soc Am. 89, 1306-1313 (1991)]. This degradation, termed "interference," was reduced by presenting the interferer continuously. In the present study, the amount of such interference was measured when the target was masked by either a broadband or a narrow-band (100-Hz-wide) noise. The narrow-band noise produced a relatively large masking-level difference, thereby allowing about 10 dB of interference to be observed. In other conditions, the interferer was turned on (temporally "fringed") prior to the target. The presence and duration of a forward fringe of the interferer did not reduce the interference, even for forward fringes of 320 ms. This result is consistent with those of Woods and Colburn [W. S. Woods and H. S. Colburn, J. Acoust Soc. Am. 91, 2894-2902 (1992)] who measured the detectability of interaural delay of low-frequency tones. The data from both studies indicate that binaural interference is observed even under conditions where interferers and targets are perceptually segregated in the sense that listeners hear more than one sound object.

Audiometry, Pure-Tone↗

Differential c-jun expression in response to tumor promoters in JB6 cells sensitive or resistant to neoplastic transformation.

The activity of AP-1, a trans-acting transcription factor, is stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. TPA and EGF also promote neoplastic transformation only in P+ cells. Thus, it has been proposed that AP-1-dependent gene expression is involved in determining sensitivity to tumor promotion. This paper explores the possible basis for the differential inducibility of AP-1 activity in P+ and P- JB6 cells, focusing in particular on the regulation of expression of the components of the AP-1 complex at the mRNA level. The expression of jun and fos gene family members, which make up the AP-1 complex, can be stimulated by serum and a number of growth factors, including EGF, and by TPA. Therefore, the possibility that differential expression of one or more forms of jun or fos contributes to the differential AP-1 activity was considered. The data presented here demonstrate both similarities and differences in the basal and TPA- or EGF-induced levels of fos and jun family members between P+ and P- cells. The most striking observation was that the overall TPA- and EGF-induced levels of jun but not fos expression were higher in P+ cells. This suggests that tumor promoter-regulated c-jun expression may contribute to the differential AP-1 activation observed in these cells and may be important in determining sensitivity to promotion of neoplastic transformation.

Animals↗

12-O-tetradecanoylphorbol-13-acetate--induced levels of AP-1 proteins: a 46-kDa protein immunoprecipitated by anti-fra-1 and induced in promotion-resistant but not promotion-sensitive JB6 cells.

Neoplastic transformation and transcriptional activation by activator protein-1 (AP-1) complex are stimulated by tumor-promoting agents in promotion-sensitive (P+) but not promotion-resistant (P-) mouse epidermal JB6 cells in culture. This implicates AP-1 as a specific regulator of signal transduction pathways in the promotion phase of neoplastic transformation. We therefore hypothesized that the defective P- responsiveness may be due to limiting levels of AP-1 protein components in those cells. In this investigation, steady-state levels of AP-1 protein components were measured by immunoprecipitating proteins from 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated P+ and P- cells to discern what may limit the AP-1 response. Whereas the AP-1 proteins junB, junD, and fosB did not show differential basal or TPA-inducible levels in P+ and P- cells, a 46-kDa species precipitated by anti-fra-1 antibody was TPA-inducible in P- cells but not in P+ cells, and c-jun protein was present at higher levels in TPA-treated and untreated P+ cells than in P- cells. These data raise the possibility that the 46-kDa fra-1-related protein may be a negative modulator of AP-1 activity and suggest that elevated levels of this 46-kDa species and limiting levels of c-jun may significantly impair AP-1 function or transformation response in P- cells or both.

Amino Acid Sequence↗

Detection of antiphasic sinusoids added to the envelopes of high-frequency bands of noise.

Listeners' sensitivities to antiphasic sinusoids added to the envelopes of high-frequency bands of noise were measured as a function of the frequency of the sinusoid and the bandwidth of the masking noise. The stimuli were constructed such that the added sinusoid produced interaural intensive differences (IIDs) that fluctuated at a rate that was equal to the frequency of the sinusoid and was independent of the bandwidth of the masking noise. The data indicated that performance was relatively unaffected by the rate of modulation for rates between 5 and 160 Hz. Greater rates of modulation resulted in substantial degradations of performance. The results are pertinent to Zurek and Durlach's (1987) suggestions concerning the relatively small binaural masking-level differences typically measured with high-frequency signals and broadband maskers in the N0S pi configuration. Specifically, it appears that listeners' performance is greatly affected by an insensitivity to rapidly fluctuating IIDs but is relatively unaffected by any 'spectral interference' produced by masking energy beyond the monaural critical band. Interestingly, the data corroborate Grantham's (1984) insightful proposal that the binaural system may possess two independent averaging mechanisms, one for the processing of interaural temporal disparities (ITDs) and the other for the processing of IIDs.

Acoustic Stimulation↗

Discrimination of interaural envelope correlation and its relation to binaural unmasking at high frequencies.

Listeners' sensitivity to interaural correlation of the envelope of high-frequency waveforms and whether such sensitivity might account for detectability in a masking-level difference paradigm were assessed. Thresholds of interaural envelope decorrelation (from a reference correlation of 1.0) were measured for bands of noise centered at 4 kHz and bandwidths ranging from 50-1600 Hz. Decorrelation of the envelope was achieved by "mixing" two independent narrow-band noises. Separately, with the same listeners, NoSo and NoS pi detection thresholds were measured for maskers of the same center frequency and bandwidths. For bandwidths of noise up to about 400 Hz, listeners were similarly sensitive to interaural decorrelation in both types of task. However, for bandwidths greater than 400 Hz or so, while sensitivity in the discrimination task was unaffected, sensitivity was reduced in the NoS pi conditions. Additional data suggested that listeners were able to maintain their sensitivity independent of bandwidth in the discrimination task by focusing on binaural information within select spectral regions of the stimuli.

Acoustic Stimulation↗

Complications of home parenteral nutrition.

The complications associated with home parenteral nutrition (HPN) and their relationship to length of therapy were studied. The medical records of 56 patients treated with HPN (age range, 6 months to 82 years) were retrospectively reviewed to study complications associated with HPN. Of the 56 study patients, 30 (53.6%) had complications related to HPN, 18 (32.1%) had complications not related to HPN, and 8 (14.3%) had no complications. Of the 365 total complications noted, 125 (34.2%) were related to HPN. The mean +/- S.D. interval between initiation of HPN and occurrence of a complication was 1.25 +/- 1.73 years (mean +/- S.D.). Patients were more likely to have fluid or electrolyte complications or glucose intolerance in the first year of therapy and catheter-related complications later in the course of treatment. The first episode of septicemia occurred 2.1 +/- 1.8 years (mean +/- S.D.) after the initiation of HPN. The risk of developing catheter-related septicemia was higher for patients on long-term HPN therapy and for young patients. Patients receiving HPN should be carefully monitored for complications such as fluid and electrolyte abnormalities and glucose intolerance, which commonly occur early in the course of therapy; later complications of HPN include catheter-related infection, thrombosis, and breakage or dislodgement.

Adolescent↗

Measurement and specification of the envelope correlation between two narrow bands of noise.

Empirical measurements show that when two independent, narrow-band, Gaussian noises are 'mixed' or combined according to the method specified by Licklider and Dzendolet (1948) [Science, 107, 121-124], the correlation coefficient between the envelopes (rExy) of the two resulting narrow-band noises is approximately equal to the square of the correlation between the waveforms (rxy). This relation also holds for waveform correlations produced by de-correlating two perfectly correlated noises by the addition of a sinusoid (at the center frequency) that is phase-reversed (N0S pi). This is true so long as the signal-to-noise ratio is small. A method is detailed whereby any desired rExy may be achieved with reasonable accuracy between two noises of the same or different center-frequency. This method may prove particularly useful in the study of listeners' sensitivities to dissimilarities in the envelope fluctuation of bands of noise occupying discrete spectral loci, a topic currently of interest. It is hoped that the empirical relations between rxy and rExy may stimulate efforts to derive or locate analytic expressions that relate the two.

Hearing↗

Spectral interference in a binaural detection task.

Several investigations suggest that sensitivity to changes in interaural disparities within select spectral regions may be degraded by the presence of energy at other, even remote, spectral regions. This study assessed whether similar degradations would be observed in an MLD paradigm. Detection thresholds were measured for NoSo and NoS pi. The signal, an 800-Hz tone (100-ms), was presented in continuous, broadband noise. Thresholds were also measured in the presence of a 400-Hz tone (the interferer) presented with an interaural phase disparity of 180 degrees and gated simultaneously with the signal or presented continuously. NoS pi thresholds increased by about 7 dB with the gated interferer at 80 dB SPL. Smaller increases were observed with lower levels of the interferer. Presenting the interferer continuously reduced substantially its effect. NoSo thresholds were affected only slightly by the interferer. Reversing the roles of the signal and interferer (400-Hz signal, 800-Hz interferer) led to smaller, but reliable degradations in performance. Diotic interferers had, in general, smaller effects on performance. The possible relation between the mechanisms that produce interference and those that foster an ability to segregate sources of sound is discussed.

Adult↗

Lateralization of low-frequency tones: relative potency of gating and ongoing interaural delays.

Several types of interaural delay can affect the lateral position of binaural signals. Delays can occur within the gating (onset and/or offset) or ongoing portions of the signal, or both. Extent of laterality produced by each of these delays was measured for low-frequency tones with an acoustic pointing task. Relative potency was assessed by presenting the delays singly or in combinations (where the types of delay were consistent or in opposition). Rise/decay time, duration, and frequency of the tonal targets were also varied. The major finding was that ongoing delays were much more potent than gating delays in determining extent of laterality. Gating delays were most effective when the interaural phase of the ongoing portion of the tones was more or less ambiguous with respect to which ear was leading. Many of our findings are qualitatively well described by considering properties of patterns of activity produced within a cross-correlation network by such interaurally delayed signals.

Acoustic Stimulation↗

Gene regulation and genetic susceptibility to neoplastic transformation: AP-1 and p80 expression in JB6 cells.

The mouse epidermal JB6 cell system consists of clonal genetic variants that are sensitive (P+) or resistant (P-) to the promotion of neoplastic transformation by phorbol esters and other tumor-promoting agents. P+ cells display AP-1-dependent phorbol-ester-inducible transactivation of gene expression, whereas P- cells have a defect in transactivation. Transfection of promotion sensitivity gene pro-1 into P- cells reconstituted both P+ phenotype and AP-1-dependent phorbol-ester-inducible transactivation. P- and P+ cells exhibited induction of c-jun and c-fos messenger RNA levels by phorbol ester, but P- cells had significantly lower basal and induced levels of jun mRNA than P+ cells. Basal and induced levels of c-jun protein were significantly lower in P- cells as well. Differences in levels the 80-kDa pI 4.5 protein p80 were also observed in JB6 cells as a function of preneoplastic progression; high levels of p80 protein and mRNA were observed in P- cells, intermediate levels in P+ cells, and negligible levels were observed in transformed derivatives of JB6 cells. Phorbol ester treatment induced phosphorylation but not synthesis of p80. These data are consistent with the hypotheses that AP-1 is required in the signal transduction pathway for promotion of neoplastic transformation by tumor promoter, that pro genes may control AP-1 activity, that threshold levels of Jun mRNA and protein may play a role in transactivation and promotion sensitivity, and that the p80 protein in JB6 cells may behave in vivo as a suppressor of cellular transformation.

Amino Acid Sequence↗

Detectability of interaural delays over select spectral regions: effects of flanking noise.

Zurek [P. M. Zurek, J. Acoust. Soc. Am. Suppl. 1 78, S18 (1985)] noted what he termed "spectral dominance" in sensitivity to interaural delay for broadband stimuli. He found that interaural delays presented solely within high-frequency spectral regions were difficult, if not impossible, to detect in the presence of spectrally flanking, gated, diotic noise. In order to see if spectral dominance is a general result of the processing of interaural delays in broadband stimuli, similar experiments were conducted utilizing both gated and continuous flanking noises that were interaurally identical (diotic) or completely uncorrelated. Beyond replicating Zurek's basic findings, the data strongly suggest that the processing of interaural delays was largely unaffected when the flanking sounds were continuous and diotic. When the flanking sounds were interaurally uncorrelated, sensitivity was affected, but not drastically, for both gated and continuous conditions. Consequently, it appears that any inability to cope with conflicting interaural cues across spectral regions may be observed only under restricted conditions.

Acoustic Stimulation↗

On the use of adaptive procedures in binaural experiments.

Adaptive psychophysical procedures have been routinely used in monaural experiments for many years, but only sparsely used in binaural experiments. In this letter, (1) the increasing use of adaptive procedures in binaural experiments is documented; (2) factors that determine their appropriateness are discussed; and (3) data that attest to their usefulness are presented.

Adaptation, Physiological↗