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Biomedical subjects

C A Fowler

Publications and source records attributed to C A Fowler.

At least 19 recordsLinked to original sources
PubMed2000

Rapid determination of protein folds using residual dipolar couplings.

Over the next few years, various genome projects will sequence many new genes and yield many new gene products. Many of these products will have no known function and little, if any, sequence homology to existing proteins. There is reason to believe that a rapid determination of a protein fold, even at low resolution, can aid in the identification of function and expedite the determination of structure at higher resolution. Recently devised NMR methods of measuring residual dipolar couplings provide one route to the determination of a fold. They do this by allowing the alignment of previously identified secondary structural elements with respect to each other. When combined with constraints involving loops connecting elements or other short-range experimental distance information, a fold is produced. We illustrate this approach to protein fold determination on (15)N-labeled Eschericia coli acyl carrier protein using a limited set of (15)N-(1)H and (1)H-(1)H dipolar couplings. We also illustrate an approach using a more extended set of heteronuclear couplings on a related protein, (13)C, (15)N-labeled NodF protein from Rhizobium leguminosarum.

Acyl Carrier Protein↗
PubMed2000

Insulin-like growth factor binding protein-3 (IGFBP-3) potentiates paclitaxel-induced apoptosis in human breast cancer cells.

Variability in response to chemotherapy is poorly understood. Paclitaxel-induced apoptosis was assessed in human Hs578T breast cancer cells, using the MTT assay, cell counting, morphological features and flow cytometry. Pre-dosing cells with non-glycosylated insulin-like growth factor binding protein-3 (ngIGFBP-3) had no effect on the cells per se but accentuated paclitaxel-induced apoptosis. The apoptotic pathway was further examined by measuring caspase-3 activity in cell lysates at time points over 48 hr after dosing with paclitaxel. Activity increased significantly, and Western immunoblots for caspase-3 in conditioned media showed that the inactive precursor decreased after incubation with paclitaxel. Endogenous production of IGFBP-3 by the cells after incubation with paclitaxel was evaluated using Western ligand blotting, specific IGFBP-3 immunoblotting and radioimmunoassay. Paclitaxel increased endogenous IGFBP-3, which was further increased if the cells had been pre-dosed with ngIGFBP-3. These findings suggest that IGFBP-3 may be an important modulator of paclitaxel-induced apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Direct measurement of 1H-1H dipolar couplings in proteins: a complement to traditional NOE measurements.

An intensity-based constant-time COSY (CT-COSY) method is described for measuring 1H-1H residual dipolar couplings of proteins in weakly aligned media. For small proteins, the overall sensitivity of this experiment is comparable to the NOESY experiment. In cases where the 1H-1H distances are defined by secondary structure, such as 1H(alpha)-1H(N) and 1H(N)-1H(N) sequential distances in alpha-helices and beta-sheets, these measurements provide useful orientational constraints for protein structure determination. This experiment can also be used to provide distance information similar to that obtained from NOE connectivities once the angular dependence is removed. Because the measurements are direct and non-coherent processes, such as spin diffusion, do not enter, the measurements can be more reliable. The 1/r3 distance dependence of directly observed dipolar couplings, as compared with the 1/r6 distance dependence of NOEs, also can provide longer range distance information at favorable angles. A simple 3D, 15N resolved version of the pulse sequence extends the method to provide the improved resolution required for application to larger biomolecules.

Acyl Carrier Protein↗
PubMed2000

Contrast effects do not underlie effects of preceding liquids on stop-consonant identification by humans.

These experiments explored the claim by A. Lotto and K. Kluender (1998) that frequency contrast explains listeners' compensations for coarticulation in the case of liquid consonants coarticulating with following stops. Evidence of frequency contrast in experiments that tested for it directly was not found, but Lotto and Kluender's finding that high- and low-frequency precursor tones can produce contrastive effects on stop-consonant judgments were replicated. The effect depends on the amplitude relation of the tones to the third formant (F3) of the stops. This implies that the tones mask F3 information in the stop consonants. It is unknown whether liquids and following stops in natural speech are in an appropriate intensity relation for masking of the stop. A final experiment, exploiting the McGurk effect, showed compensation for coarticulation by listeners when neither frequency contrast nor masking can be the source of the compensations.

Humans↗
PubMed2000

Perceptual parsing of acoustic consequences of velum lowering from information for vowels.

Three experiments were designed to investigate how listeners to coarticulated speech use the acoustic speech signal during a vowel to extract information about a forthcoming oral or nasal consonant. A first experiment showed that listeners use evidence of nasalization in a vowel as information for a forthcoming nasal consonant. A second and third experiment attempted to distinguish two accounts of their ability to do so. According to one account, listeners hear nasalization in the vowel as such and use it to predict that a forthcoming nasal consonant is nasal. According to a second, they perceive speech gestures and hear nasalization in the acoustic domain of a vowel as the onset of a nasal consonant. Therefore, they parse nasal information from a vowel and hear the vowel as oral. In Experiment 2, evidence in favor of the parsing hypothesis was found. Experiment 3 showed, however, that parsing is incomplete.

Female↗
PubMed1998

On the relevance of locus equations for production and perception of stop consonants.

We examined the possible relevance of locus equations to human production and perception of stop consonants. The orderly output constraint (OOC) of Sussman, Fruchter, and Cable (1995) claims that humans have evolved to produce speech such that F2 at consonant release and F2 at vowel midpoint are linearly related for consonants so that developing perceptual systems can form representations in an F2ons-by-F2vowel space. The theory claims that this relationship described by locus equations can distinguish consonants, and that the linearity of locus equations is captured in neural representations and is thus perceptually relevant. We investigated these claims by testing how closely locus equations reflect the production and perception of stop consonants. In Experiment 1, we induced speakers to change their locus equation slope and intercept parameters systematically, but found that consonants remained distinctive in slope-by-intercept space. In Experiment 2, we presented stop-consonant syllables with their bursts removed to listeners, and compared their classification error matrices with the predictions of a model using locus equation prototypes and with those of an exemplar-based model that uses F2ons and F2vowel, but not locus equations. Both models failed to account for a large proportion of the variance in listeners' responses; the locus equation model was no better in its predictions than the exemplar model. These findings are discussed in the context of the OOC.

Adult↗
PubMed1997

Perceiving the causes of coarticulatory acoustic variation: consonant voicing and vowel pitch.

Coarticulatory acoustic variation is presumed to be caused by temporally overlapping linguistically significant gestures of the vocal tract. The complex acoustic consequences of such gestures can be hypothesized to specify them without recourse to context-sensitive representations of phonetic segments. When the consequences of separate gestures converge on a common acoustic dimension (e.g., fundamental frequency), perceptual parsing of the acoustic consequences of overlapping spoken gestures, rather than associations of acoustic features, is required to resolve the distinct gestural events. Direct tests of this theory were conducted. These tests revealed mutual influences of (1) fundamental frequency during a vowel on prior consonant perception, and (2) consonant identity on following vowel stress and pitch perception. The results of these converging tests lead to the conclusion that speech perception involves a process in which acoustic information for coarticulated gestures is parsed from the stream of speech.

Humans↗
PubMed1997

Intrinsic fO differences in spoken and sung vowels and their perception by listeners.

We explore how listeners perceive distinct pieces of phonetic information that were conveyed in parallel by the fundamental frequency (fO) contour of spoken and sung vowels. In a first experiment, we measured differences in fO of /i/ and /a/ vowels spoken and sung by unselected undergraduate participants. Differences in "intrinsic fO" (with fO of /i/ higher than of /a/) were present in spoken and sung vowels; however, differences in sung words were smaller than those in spoken vowels. Four experiments tested a hypothesis that listeners would not hear the intrinsic fO differences as differences in pitch on the vowel, because they provide information, instead, for production of a closed or open vowel. The experiments provide clear evidence of "parsing" of intrinsic fO from the fO that contributes to perceived vowel pitch. However, only some conditions led to an estimate of the magnitude of parsing that closely matched the magnitude of produced intrinsic fO differences.

Humans↗
PubMed1996

Listeners do hear sounds, not tongues.

The paper first distinguishes the two perceptual theories, the motor theory and the theory of direct perception, that nearly agree in the claim that listeners to speech perceive vocal tract gestures. Next it justifies the claim of the direct realist theory that listeners perceive gestures and consider some experimental evidence in its favor. Finally it addresses evidence and arguments judged by Ohala to disconfirm the theory. The argument is made that most of the evidence put forward by Ohala is irrelevant to a distinction between theories that we perceive acoustic signals and theories that we perceive gestures. The arguments are inaccurate or highly selective in the data upon which they draw.

Gestures↗
PubMed1994

Invariants, specifiers, cues: an investigation of locus equations as information for place of articulation.

This experiment explored the information for place of articulation provided by locus equations--equations for a line relating the second formant (F2) of a vowel at midpoint of F2 of the formant at consonant-vowel (CV) syllable onset. Locus equations cue place indirectly by quantifying directly the degree of coarticulatory overlap (coarticulation resistance) between consonant and vowel. Coarticulation resistance is correlated with place. The experiment tested predictions that when coarticulation resistance varies due to properties of the consonant other than place of articulation (in particular, due to manner of articulation), locus equations would not accurately reflect consonantal place of articulation. These predictions were confirmed. In addition, discriminant analyses, using locus equation variables as classifiers, were generally unsuccessful in classifying a set of consonants representing six different places of articulation. I conclude that locus equations are unlikely to provide useful place information to listeners.

Adult↗
PubMed1994

Hemispheric contributions to the integration of visual and auditory information in speech perception.

Differential hemispheric contributions to the perceptual phenomenon known as the McGurk effect were examined in normal subjects, 1 callosotomy patient, and 4 patients with intractable epilepsy. Twenty-five right-handed subjects were more likely to demonstrate an influence of a mouthed word on identification of a dubbed acoustic word when the speaker's face was lateralized to the LVF as compared with the RVF. In contrast, display of printed response alternatives in the RVF elicited a greater percentage of McGurk responses than display in the LVF. Visual field differences were absent in a group of 15 left-handed subjects. These results suggest that in right-handers, the two hemispheres may make distinct contributions to the McGurk effect. The callosotomy patient demonstrated reliable McGurk effects, but at a lower rate than the normal subjects and the epileptic control subjects. These data support the view that both the right and left hemisphere can make significant contributions to the McGurk effect.

Adult↗
PubMed1992

Fundamental frequency declination is not unique to human speech: evidence from nonhuman primates.

In human speech, declination of the fundamental frequency (F0) of the voice spans coherent units of an utterance and, therefore, signals where units begin and end. A rapid final fall at the end of an utterance provides a further indication of an utterance's ending. The occurrence of declination is sufficiently widespread across languages that several investigators have suggested it as a language universal. Language universals may be universal because they are part of a species-specific specialization for language or, alternatively, they may constitute conventionalizations of natural dispositions of the vocal tract that may serve a communicative function. Evidence is offered favoring the latter account for declination and the final fall by showing that vocal productions of vervet monkeys (Cercopithecus aethiops) and rhesus macaques (Macaca mulatta) show declination, and vervets show clear evidence of a final fall. Interestingly, the fall in F0 may serve some communicative role in the vocal exchanges of vervets and rhesus, analogous to its signalling function in human language.

Acoustics↗
PubMed1992

Declination of supralaryngeal gestures in spoken Italian.

Two experiments investigate a weakening of supralaryngeal gestures in an utterance, analogous in some ways to declination of fundamental frequency and amplitude. In one experiment, acoustic measures revealed progressive centralization of stressed /i/, /a/ and /u/ left to right in trisyllabic utterances read by Tuscan subjects. A second experiment, using speakers of a different (Northern) variety of Standard Italian, found reduction in jaw opening for stressed /a/ left to right, but generally failed to replicate a centralization of /i/. This experiment further suggested that the progressive weakening of supralaryngeal gestures is largely a phrase level rather than a word level phenomenon. Both experiments found a different, V-shaped, pattern of opening to be generally characteristic of unstressed syllables.

Adult↗
PubMed1992

Audiovisual integration in perception of real words.

Three experiments follow up on Easton and Basala's (1982) report that the "McGurk effect" (an influence of a visibly mouthed utterance on a dubbed acoustic one) does not occur when utterances are real words rather than nonsense syllables. In contrast, with real-word stimuli, Easton and Basala report a strong reverse effect whereby a dubbed soundtrack strongly affects identification of lipread words. In Experiment 1, we showed that a strong McGurk effect does obtain when dubbed real words are discrepant with observed words in consonantal place of articulation. A second experiment obtained only a weak reverse effect of dubbed words on judgments of lipread words. A final experiment was designed to provide a sensitive test of effects of lipread words on judgments of heard words and of heard words on judgments of lipread words. The findings reinforced those of the first two experiments that both effects occur, but, with place-of-articulation information discrepant across the modalities, the McGurk effect is strong and the reverse effect weak.

Attention↗
PubMed1991

Listening with eye and hand: cross-modal contributions to speech perception.

Three experiments investigated the "McGurk effect" whereby optically specified syllables experienced synchronously with acoustically specified syllables integrate in perception to determine a listener's auditory perceptual experience. Experiments contrasted the cross-modal effect of orthographic on acoustic syllables presumed to be associated in experience and memory with that of haptically experienced and acoustic syllables presumed not to be associated. The latter pairing gave rise to cross-modal influences when Ss were informed that cross-modal syllables were paired independently. Mouthed syllables affected reports of simultaneously heard syllables (and vice versa). These effects were absent when syllables were simultaneously seen (spelled) and heard. The McGurk effect does not arise from association in memory but from conjoint near specification of the same causal source in the environment--in speech, the moving vocal tract producing phonetic gestures.

Adult↗
PubMed1991

Audiovisual investigation of the loudness-effort effect for speech and nonspeech events.

There is some evidence that loudness judgments of speech are more closely related to the degree of vocal effort induced in speech production than to the speech signal's surface-acoustic properties such as intensity. Other researchers have claimed that speech loudness can be rationalized simply by considering the acoustic complexity of the signal. Because vocal effort can be specified optically as well as acoustically, a study to test the effort-loudness hypothesis was conducted that used conflicting audiovisual presentations of a speaker that produced consonant-vowel syllables with different efforts. It was predicted that if loudness judgments are constrained by effort perception rather than by simple acoustic parameters, then judgments ought to be affected by visual as well as auditory information. It is shown that loudness judgments are affected significantly by visual information even when subjects are instructed to base their judgments only on what they hear. A similar (though less pronounced) patterning of results is shown for a nonspeech "clapping" event, which attests to the generality of the loudness-effort effect previously thought to be special to speech. Results are discussed in terms of auditory, fuzzy logical, motor, and ecological theories of speech perception.

Adult↗
PubMed1991

Auditory perception is not special: we see the world, we feel the world, we hear the world.

The literature on "contrast" provides no evidence that durational contrast should occur in the speech and nonsence signals used in research cited by Diehl et al. [J. Acoust. Soc. Am. 89, 2905-2909 (1991)]. Moreover, there is evidence that, in comparable signals, it does not occur. Accordingly, their own account of the collection of findings on rate normalization is not viable. Their comments on my research do not imperil my interpretation of it or challenge my criticism that classification judgments of acoustically analogous speech and nonsense signals do not permit interpretation, by themselves, in terms of underlying auditory-system mechanisms. Their arguments that in auditory perception, uniquely, we hear proximal stimulation, not its physical causal sources, is implausible. Their theoretical perspective generally, I argue, is unrealistic.

Auditory Perception↗