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Amyloid formation has been implicated in the pathology of over 20 human diseases, but the rational design of amyloid inhibitors is hampered by a lack of structural information about amyloid-inhibitor complexes. We use isotope labelling and two-dimensional infrared spectroscopy to obtain a residue-specific structure for the complex of human amylin (the peptide responsible for islet amyloid formation in type 2 diabetes) with a known inhibitor (rat amylin). Based on its sequence, rat amylin should block formation of the C-terminal β-sheet, but at 8 h after mixing, rat amylin blocks the N-terminal β-sheet instead. At 24 h after mixing, rat amylin blocks neither β-sheet and forms its own β-sheet, most probably on the outside of the human fibrils. This is striking, because rat amylin is natively disordered and not previously known to form amyloid β-sheets. The results show that even seemingly intuitive inhibitors may function by unforeseen and complex structural processes.

The human islet amylin polypeptide is produced along with insulin by pancreatic islets. Under some circumstances, amylin can aggregate to form amyloid fibrils, whose presence in pancreatic cells is a common pathological feature of Type II diabetes. A growing body of evidence indicates that small, early stage aggregates of amylin are cytotoxic. A better understanding of the early stages of the amylin aggregation process and, in particular, of the nucleation events leading to fibril growth could help identify therapeutic strategies. Recent studies have shown that, in dilute solution, human amylin can adopt an α-helical conformation, a β-hairpin conformation, or an unstructured coil conformation. While such states have comparable free energies, the β-hairpin state exhibits a large propensity towards aggregation. In this work, we present a detailed computational analysis of the folding pathways that arise between the various conformational states of human amylin in water. A free energy surface for amylin in explicit water is first constructed by resorting to advanced sampling techniques. Extensive transition path sampling simulations are then employed to identify the preferred folding mechanisms between distinct minima on that surface. Our results reveal that the α-helical conformer of amylin undergoes a transformation into the β-hairpin monomer through one of two mechanisms. In the first, misfolding begins through formation of specific contacts near the turn region, and proceeds via a zipping mechanism. In the second, misfolding occurs through an unstructured coil intermediate. The transition states for these processes are identified. Taken together, the findings presented in this work suggest that the inter-conversion of amylin between an α-helix and a β-hairpin is an activated process and could constitute the nucleation event for fibril growth. [ABSTRACT FROM AUTHOR]

Recently, novel organic glassy materials that exhibit remarkable stability have been prepared by vapor deposition. The thermophysical properties of these new 'stable' glasses are equivalent to those that common glasses would exhibit after aging over periods lasting thousands of years. The origin of such enhanced stability has been elusive; in the absence of detailed models, past studies have discussed the formation of new polyamorphs or that of nanocrystals to explain the observed behavior. In this work, an atomistic molecular model of trehalose, a disaccharide of glucose, is used to examine the properties of vapor-deposited stable glasses. Consistent with experiment, the model predicts the formation of stable glasses having a higher density, a lower enthalpy, and higher onset temperatures than those of the corresponding 'ordinary' glass formed by quenching the bulk liquid. Simulations reveal that newly formed layers of the growing vapor-deposited film exhibit greater mobility than the remainder of the material, thereby enabling a reorganization of the film as it is grown. They also reveal that 'stable' glasses exhibit a distinct layered structure in the direction normal to the substrate that is responsible for their unusual properties. [ABSTRACT FROM AUTHOR]

Evaluates the perceptual strategies of children in comparing phonemes. Measurement of the choice reaction time judgments involving possible pairs of selected English consonants; Use of multidimensional scaling techniques for speech perception data from children; Psychological proximities between stimuli.

Looks into the comparison of speech-sound production and discrimination in children with functional articulation disorders. Utilization of the Goldman-Fristoe-Woodcock Test of Auditory Discrimination; Obtainment of articulation responses from the identical word-picture stimulus items; Employment of an articulatory-based distinctive feature system; Discussion on the implications for articulation therapy.

The article presents a study of multidimensional scaling analysis of phenomic responses from hard of hearing and deaf subjects. The results of this study indicate that the deaf subjects did not utilize the feature sibilant as effectively as did the hard of hearing subjects. Since the sibilants are primarily high frequency in nature, the higher degree of hearing impairment for the profoundly deaf subject may account for the difference in the perception of sibilants between this group and that of the hard of hearing. Since the perceptual spaces and their interpretations were in considerable agreement across the language groups studied here, it is possible that the utilization of the features proposed here would assist in breaking the language barriers for those in search of a statistically, phonologically, and perceptually relevant tool for habilitation or rehabilitation of persons with severe hearing impairments.

The purpose of this study was to investigate acoustic attributes of the voices of preadolescent children as a function of sex and age. Voice samples of the sustained vowel /a/ were obtained from 180 children, 15 males and 15 females at ages five, six, seven, eight, nine, and ten years. Measurement of fundamental frequency was obtained to determine sex-related differences and age-related trends. This acoustic analysis revealed that a male/female difference in fundamental frequency emerged by age seven, and that fundamental frequency decreased significantly in male children only, between age five and age ten. [ABSTRACT FROM AUTHOR]

This paper is a sequel to a study which showed that the dominant dimension for perceptual discrimination among normal voices was the male-female categorization and which also suggested that discrimination within the male-female categories utilized distinct dimensions. The present study eliminates the male-female axis by treating the gender groups separately and making the within-category dimensions available for more sensitive analysis. The purpose was to determine the number and nature of perceptual parameters needed to explain judgments of voice similarity depending on talker sex and whether the stimulus sample was a sustained vowel or a short phrase. The similarity judgments were submitted to multidimensional analysis via INDSCAL and the resulting dimensions were interpreted in terms of available acoustic measures and unidimensional voice-quality ratings of pitch, breathiness, hoarseness, nasality, and effort. The decisions of the listeners appeared to be influenced by both the sex of the speaker and the stimulus sample, although fundamental frequency (f0), was important for all judgments. Aside from the f0 dimensions, judgments concerning male voices were related to vocal tract parameters, while similarity judgments of female voices were related to perceived glottal/vocal tract differences. Formant structure was apparently important in judging the similarity of vowels for both sexes while perceptual glottal/temporal attributes may have been used as cues in the judgments of phrases. [ABSTRACT FROM AUTHOR]

The role distinctive features played in the identification of 21 dichotically presented syllable initial English consonants was evaluated. Results were analyzed for the entire stimulus set and for various intra- and inter-manner class comparisons. Consistent with previous dichotic studies of stops alone, stops as a subgroup showed a large right ear advantage, a high incidence of blend errors, and greater accuracy in identification when the competing stimuli contrasted on one (rather than two) distinctive features. Results for manner classes other than stops, for inter-manner comparisons and for the total stimulus set indicated increased correct identification with increasing numbers of distinctive feature differences between the two syllables. Analysis of error patterns revealed that, in addition to the stops, continuants, and stop-continuant, stop-affricate, and stop-nasal pairs revealed significant numbers of blend errors. Error responses also showed a tendency for unmarked feature specifications to predominate significantly over marked feature specifications. Finally, the magnitude of the right ear advantage varied significantly as a function of manner class, but not as a function of number of feature contrasts. [ABSTRACT FROM AUTHOR]

This study investigates and acoustically defines some of the perceptual parameters used to distinguish among normal male and female voices. Twenty normal speaking subjects, ten male and ten female, produced speech segments which were paired, randomized, and presented to ten listener judges. The judges rated the similarity of all combinations of voices on a seven-point scale, and these similarities were analyzed by a multidimensional analysis technique, INDSCAL. For each speaker, eight acoustical measures were obtained, and psychophysical ratings of four commonly used descriptive terms were made by ten speech pathologists. These measurements and ratings provided the interpretation of the INDSCAL solution and were also submitted to correlational analyses. The results indicate that, when distinguishing among the voices, the judges gave the greatest weight to the male versus female dimension and its acoustical correlates. The results of both the INDSCAL analysis and the correlational analyses suggest that listeners may use different perceptual strategies to classify male voices than they use to classify female ones. [ABSTRACT FROM AUTHOR]

This study demonstrates the application of a multidimensional scaling technique, known as INDSCAL, to determine the perceptual attributes of a group of non-normal voices. In this study, equal-appearing interval scale was used to obtain judgments of similarity for 20 speakers sustaining a vowel. For each speaker, six physical and three psychophysical measures were also obtained and used to interpret the INDSCAL solution. A five-dimensional solution was found to be the most appropriate solution for explaining the variance. The findings of the INDSCAL analysis suggest that there exist distinct perceptual features of the abnormal voice which have physical and psychophysical correlates. The strengths of the underlying dimensions of the voices appear to indicate that multidimensional scaling will be a valuable tool in the diagnosis of voice abnormalities. [ABSTRACT FROM AUTHOR]

Determines if the consonant substitution patterns made by children with consonant articulation problem show substantial regularity. Suggestion that substitution is governed by stability and similarity; Conclusion that the preferred substitute is the nearest fronted consonant to the sound in question.

The article cites a study which compares nonsense syllables spoken by English-speaking and Hindi speaking groups under varying conditions of sidetone, listening, and rates of reading. Results of the study indicated that the two language groups did not statistically show differences in the mean duration of the syllables nor in mean syllabic speech power. The speech duration was extended under the condition of delayed sidetone, as compared to the normal and so with the condition of normal rate of reading as compared to the fast. In the contrary, the two language groups show differences in scores that were derived from the phonetic transcriptions of verbal material.

The intelligibility of /p t k b d g/ as spoken and heard by native speakers and listeners of Hindi and English and the relationship of this intelligibility to the transitions of consonants to vowels in CV monosyllables were investigated. Phoneme boundaries were determined. A measure of intelligibility was obtained in terms of information transmitted per stimulus for four and two separate channels and a composite channel. The separate channels represented distinctive linguistic features. Redundancy was quantified through a comparison of the information transmitted by these systems. There was uniformity among the four speaking-listening groups in information transmitted at six points of temporal segmentation and in 20 different bandwidths, as well as similarity in the importance of channels. Models of linearity were set to assess information as a function of (1) time, (2) width of the frequency band, and (3) lower frequency of the frequency band. Multiple correlations of 0.83 in the case of (1), (2), and (3), of 0.83 in the case of (1) and (2), and of 0.77 in the case of (1) and (3) were found. [ABSTRACT FROM AUTHOR]

Twenty-six intervocalic consonants were recorded by three speakers of each of four languages-Hindi, English, Arabic, and Japanese-and heard by 24 speakers of each of them. The data were treated in two ways. (1) An analysis of variance indicated that listening groups differed and that consonants were unequal in their intelligibility and showed statistically significant interactions between speakers and consonants, between listeners and consonants, and among consonants, listeners, and speakers. All speakers spoke better and all listeners listened better when saying and hearing sounds of their native language. (2) A quantitative procedure employed by Miller and Nicely was adapted to ascertain which features were retained by the listeners in their error responses and whether or not these were similar from one language group to another. All consonants were classified in a binary manner in relation to each of seven channels into which the voice communication network was subdivided. The unusual outcome lay in the ranks of the seven channels in terms of the extents to which they were correctly preserved in the responses. A single rank order in this regard was duplicated for all the listening groups: (1) nasality, (2) place, (3) liquid, (4) voicing, (5) duration, (6) friction, and (7) aspiration. [ABSTRACT FROM AUTHOR]

Offers information on an intelligibility test using an electronic device called Self-Administered Intelligibility Testing-Training Unit. Background on intelligibility of speech; Development of the use of relative measures of intelligibility to assess the understandability of speakers and the effect of specific training in the skills of speaking in the U.S.; Summary of programs for the study of intelligibility that had military impetus; Result of the intelligibility test using the device.

The present study was undertaken in a context of second language instruction and relative "foreignism," foreign accent, or foreign soundingness in the American speech of foreign students. This aspect of speech can be rated reliably by panels of judges; it also relates to the speaker's relative skill in aural comprehension, and either directly or through an intermediary factor, to the durations of the vocalizations of the spoken materials of an intelligibility test. Specifically, the present study represented two levels of proficiency in aural comprehension of English among students who were entering an American university for advanced study.

Discusses the ratio between the rate of an individual's normal speech and his speech under different times of delay of his sidetone. Procedure for the experiment; Equipments used in the experiment.