Displacement affinity chromatography of protein phosphatase one (PP1) complexes

Background  

Protein phosphatase one (PP1) is a ubiquitously expressed, highly conserved protein phosphatase that dephosphorylates target protein serine and threonine residues. PP1 is localized to its site of action by interacting with targeting or regulatory proteins, a majority of which contains a primary docking site referred to as the RVXF/W motif.     

Spatial release from energetic and informational masking in a divided speech identification task

When listening selectively to one talker in a two-talker environment, performance generally improves with spatial separation of the sources. The current study explores the role of spatial separation in divided listening, when listeners reported both of two simultaneous messages processed to have little spectral overlap (limiting "energetic masking" between the messages). One message was presented at a fixed level, while the other message level varied from equal to 40 dB less than that of the fixed-level message. Results demonstrate that spatial separation of the competing messages improved divided-listening performance. Most errors occurred because listeners failed to report the content of the less-intense talker. Moreover, performance generally improved as the broadband energy ratio of the variable-level to the fixed-level talker increased. The error patterns suggest that spatial separation improves the intelligibility of the less-intense talker by improving the ability to (1) hear portions of the signal that would otherwise be masked, (2) segregate the two talkers properly into separate perceptual streams, and (3) selectively focus attention on the less-intense talker. Spatial configuration did not noticeably affect the ability to report the more-intense talker, suggesting that it was processed differently than the less-intense talker, which was actively attended.     

Binaural interference and auditory grouping

The phenomenon of binaural interference, where binaural judgments of a high-frequency target stimulus are disrupted by the presence of a simultaneous low-frequency interferer, can largely be explained using principles of auditory grouping and segregation. Evidence for this relationship comes from a number of previous studies showing that the manipulation of simultaneous grouping cues such as harmonicity and onset synchrony can influence the strength of the phenomenon. In this study, it is shown that sequential grouping cues can also influence whether binaural interference occurs. Subjects indicated the lateral position of a high-frequency sinusoidally amplitude-modulated (SAM) tone containing an interaural time difference. Perceived lateral positions were reduced by the presence of a simultaneous diotic low-frequency SAM tone, but were largely restored when the interferer was "captured" in a stream of identical tones. A control condition confirmed that the effect was not due to peripheral adaptation. The data lend further support to the idea that binaural interference is affected by processes related to the perceptual organization of auditory information. Modifications to existing grouping-based models are proposed that may help account for binaural interference effects more successfully.     

The influence of spatial separation on divided listening

If spatial attention acts like a "spotlight," focusing on one location and excluding others, it may be advantageous to have all targets of interest within the same spatial region. This hypothesis was explored using a task where listeners reported keywords from two simultaneous talkers. In Experiment 1, the two talkers were placed symmetrically about the frontal midline with various angular separations. While there was a small performance improvement for moderate separations, the improvement decreased for larger separations. However, the dependency of the relative talker intensities on spatial configuration accounted for these effects. Experiment 2 tested whether spatial separation improved the intelligibility of each source, an effect that could counteract any degradation in performance as sources fell outside the spatial spotlight of attention. In this experiment, intelligibility of individual sources was equalized across configurations by adding masking noise. Under these conditions, the cost of divided listening (the drop in performance when reporting both messages compared to reporting just one) was smaller when the spatial separation was small. These results suggest that spatial separation enhances the intelligibility of individual sources in a competing pair but increases the cost associated with having to process both sources simultaneously, consistent with the attentional spotlight hypothesis.     

Spatial unmasking of nearby pure-tone targets in a simulated anechoic environment

Detection thresholds were measured for different spatial configurations of 500- and 1000-Hz pure-tone targets and broadband maskers. Sources were simulated using individually measured head-related transfer functions (HRTFs) for source positions varying in both azimuth and distance. For the spatial configurations tested, thresholds ranged over 50 dB, primarily as a result of large changes in the target-to-masker ratio (TMR) with changes in target and masker locations. Intersubject differences in both HRTFs and in binaural sensitivity were large; however, the overall pattern of results was similar across subjects. As expected, detection thresholds were generally smaller when the target and masker were separated in azimuth than when they were at the same location. However, in some cases, azimuthal separation of target and masker yielded little change or even a small increase in detection threshold. Significant intersubject differences occurred as a result both of differences in monaural and binaural acoustic cues in the individualized HRTFs and of different binaural contributions to performance. Model predictions captured general trends in the pattern of spatial unmasking. However, subject-specific model predictions did not account for the observed individual differences in performance, even after taking into account individual differences in HRTF measurements and overall binaural sensitivity. These results suggest that individuals differ not only in their overall sensitivity to binaural cues, but also in how their binaural sensitivity varies with the spatial position of (and interaural differences in) the masker.     

Spatial cues alone produce inaccurate sound segregation: the effect of interaural time differences

To clarify the role of spatial cues in sound segregation, this study explored whether interaural time differences (ITDs) are sufficient to allow listeners to identify a novel sound source from a mixture of sources. Listeners heard mixtures of two synthetic sounds, a target and distractor, each of which possessed naturalistic spectrotemporal correlations but otherwise lacked strong grouping cues, and which contained either the same or different ITDs. When the task was to judge whether a probe sound matched a source in the preceding mixture, performance improved greatly when the same target was presented repeatedly across distinct distractors, consistent with previous results. In contrast, performance improved only slightly with ITD separation of target and distractor, even when spectrotemporal overlap between target and distractor was reduced. However, when subjects localized, rather than identified, the sources in the mixture, sources with different ITDs were reported as two sources at distinct and accurately identified locations. ITDs alone thus enable listeners to perceptually segregate mixtures of sources, but the perceived content of these sources is inaccurate when other segregation cues, such as harmonicity and common onsets and offsets, do not also promote proper source separation.     

Effect of stimulus spectrum on distance perception for nearby sources

The effects of stimulus frequency and bandwidth on distance perception were examined for nearby sources in simulated reverberant space. Sources to the side [containing reverberation-related cues and interaural level difference (ILD) cues] and to the front (without ILDs) were simulated. Listeners judged the distance of noise bursts presented at a randomly roving level from simulated distances ranging from 0.15 to 1.7 m. Six stimuli were tested, varying in center frequency (300-5700 Hz) and bandwidth (200-5400 Hz). Performance, measured as the correlation between simulated and response distances, was worse for frontal than for lateral sources. For both simulated directions, performance was inversely proportional to the low-frequency stimulus cutoff, independent of stimulus bandwidth. The dependence of performance on frequency was stronger for frontal sources. These correlation results were well summarized by considering how mean response, as opposed to response variance, changed with stimulus direction and spectrum: (1) little bias was observed for lateral sources, but listeners consistently overestimated distance for frontal nearby sources; (2) for both directions, increasing the low-frequency cut-off reduced the range of responses. These results are consistent with the hypothesis that listeners used a direction-independent but frequency-dependent mapping of a reverberation-related cue, not the ILD cue, to judge source distance.     

The extent to which a position-based explanation accounts for binaural release from informational masking

Detection was measured for a 500 Hz tone masked by noise (an "energetic" masker) or sets of ten randomly drawn tones (an "informational" masker). Presenting the maskers diotically and the target tone with a variety of interaural differences (interaural amplitude ratios and/or interaural time delays) resulted in reduced detection thresholds relative to when the target was presented diotically ("binaural release from masking"). Thresholds observed when time and amplitude differences applied to the target were "reinforcing" (favored the same ear, resulting in a lateralized position for the target) were not significantly different from thresholds obtained when differences were "opposing" (favored opposite ears, resulting in a centered position for the target). This irrelevance of differences in the perceived location of the target is a classic result for energetic maskers but had not previously been shown for informational maskers. However, this parallellism between the patterns of binaural release for energetic and informational maskers was not accompanied by high correlations between the patterns for individual listeners, supporting the idea that the mechanisms for binaural release from energetic and informational masking are fundamentally different.     

Chemo- and regioselective cyclohydrocarbonylation of alpha-keto alkynes catalyzed by a zwitterionic rhodium complex and triphenyl phosphite

alpha-Keto alkynes react with CO and H(2) in the presence of catalytic quantities of the zwitterionic rhodium complex (eta(6)-C(6)H(5)BPh(3))(-)Rh(+)(1,5-COD) and triphenyl phosphite affording either the 2-, 2(3H)-, or 2(5H)-furanones in 61-93% yields. The cyclohydrocarbonylation is readily accomplished using substrates containing alkyl, aryl, vinyl, and alkoxy groups at the acetylenic terminal, as well as a variety of primary, secondary, and tertiary alkyl, aryl, and heteroaryl groups connected to the ketone functionality. Structural and electronic properties present in the starting materials mediate the chemo- and regioselectivity of the reaction.     

Localizing nearby sound sources in a classroom: binaural room impulse responses

Binaural room impulse responses (BRIRs) were measured in a classroom for sources at different azimuths and distances (up to 1 m) relative to a manikin located in four positions in a classroom. When the listener is far from all walls, reverberant energy distorts signal magnitude and phase independently at each frequency, altering monaural spectral cues, interaural phase differences, and interaural level differences. For the tested conditions, systematic distortion (comb-filtering) from an early intense reflection is only evident when a listener is very close to a wall, and then only in the ear facing the wall. Especially for a nearby source, interaural cues grow less reliable with increasing source laterality and monaural spectral cues are less reliable in the ear farther from the sound source. Reverberation reduces the magnitude of interaural level differences at all frequencies; however, the direct-sound interaural time difference can still be recovered from the BRIRs measured in these experiments. Results suggest that bias and variability in sound localization behavior may vary systematically with listener location in a room as well as source location relative to the listener, even for nearby sources where there is relatively little reverberant energy.