The aging voice: a review, treatment data and familial and genetic perspectives.

This paper will provide a review of aspects of vocal aging within the context of general body aging and describe two data sets related to the aging voice. Data will be presented which document pre- to posttreatment improvement in select voice characteristics (sound pressure level, subglottal air pressure, thyroarytenoid laryngeal muscle activity and voice quality) following application of an intensive voice treatment program (the LSVT) to 3 individuals with aged voice. Additionally, physiological data (forced expiratory volume, visual accommodation, bone density, taste discrimination, white blood count and resting heart rate) and select perceptual (perceived age) and acoustic measures (reflecting both cycle-to-cycle and longer-term intensity and frequency stability) from 67 subjects will be reviewed from the work of Gray and colleagues to document the differential impact of the global aging process across organ systems including the aging voice.

Long-term phonatory instability in individuals with multiple sclerosis.

This paper uses a new approach to describe and quantify the long-term phonatory instability of speakers with MS. Sustained vowel phonations of 20 individuals with a definite diagnosis of multiple sclerosis (MS) and 20 age- and gender-matched individuals with normal speech were recorded. The phonations were f0 and intensity analyzed and subjected to spectral analysis using the Fast Fourier Transform. Three methods for analyzing the instabilities are presented, compared, and related to perceptual judgments: (a) coefficients of variation, (b) magnitude-based analysis of spectral energy, and (c) frequency-based analysis of spectral components. All measures reliably distinguished between individuals with MS and persons with normal speech. A single factor based on a linear discriminant analysis of the frequency-based measures was especially useful in distinguishing these groups. Critical frequency bands of instability, corresponding to wow (1-2 Hz), tremor (around 8 Hz), and flutter (17-18 Hz), distinguished the MS group from those of the control group.

Consonant-vowel interdependencies in babbling and early words: preliminary examination of a locus equation approach.

Consonant-vowel productions at two distinct stages of language development were studied in a single female child. At 12 months canonical babbling syllables (N = 144) identified by a panel of listeners as comprising [bV], [dV], and [gv] tokens were acoustically analyzed by measuring F2 transition onset and F2 midvowel frequencies and plotting their relationship as locus equations for each stop category. A regression analysis performed on these scatterplots revealed differential slopes and y-intercepts as a function of stop place. The same analysis was performed 9 months later on CV utterances (N = 243) produced as syllable-initial segments of real words by the same child. Whereas labial and velar locus equation parameters moved toward more adult-like values, alveolar slope and y-intercept moved away from adult values and more in the direction of decreased coarticulation between vowel and consonant. There was greater scatter of data points around the regression line for production of words compared to babbling. These results are compared to locus equations obtained from 3-5-year-olds and adults. Locus equations appear to be useful as an empirical developmental probe to document how CV productions gradually approach adult categorical standards.

Formoffa: An automated formant, moment, fundamental frequency, amplitude analysis of normal and disordered speech.

A system for semi-automatic, multi-parameter acoustic analysis is described. The system, called FORMOFFA (For = FORmants, Mo = MOments, FF = Fundamental Frequency, A = Amplitude), operates on a PC microcomputer by adaptations of commercially available software. Data displays include a deterministic time record of instantaneous values, and an ergodic time-compressed distribution. In this report the technique is developed with a one-word example, and some measurement and reliability issues are described. The analysis possibilities are then illustrated with several applications: (1) segmental analysis of normal speech, (2) acoustic assessment of the effects of a progressive neurological disease (amyotrophic lateral sclerosis) on sentence production, (3) acoustic study of palatal lift management of a patient with traumatic brain injury, and (4) phonetic assessment of word production by a subject with dysarthria. Although the current technique is recommended as a research tool, this kind of analysis promises several advantages for clinical application, including semi-automaticity, efficiency, parsimony, and relevance to both segmental and suprasegmental levels of analysis.

Acoustic correlates of stress in young children's speech.

This study examined the acoustic correlates of stress in children's productions of familiar words. Previous research has employed experimental words rather than familiar words to examine children's phonetic marking of stress, or has not adequately controlled for phonetic environment. Subjects in this study included 22 children, aged 18-30 months, and 6 adults. Fundamental frequency, duration, and amplitude measures were extracted from stressed and unstressed syllables in two types of comparisons: one that controlled phonetic environment and syllable position (interword) and one that measured the relative effects of stress within the same word (intraword). When the tokens were analyzed on the basis of target stress pattern, results revealed no differences between adults and children in their acoustic marking of stress. Listener judgments showed that approximately 30% of children's two-syllable productions were coded unreliably or were perceived as inaccurately stressed. Overall findings indicate that children control fundamental frequency, amplitude, and duration to derive perceptually identifiable stress contrasts in the majority of their productions but they are not completely adult-like in their marking of stress.

Phrasing in prelinguistic vocalizations.

Phrasing is a universal characteristic of human communication, and the present investigation explored its developmental roots in nonvegetative, prelinguistic vocalizations. Adult judges identified a hierarchical arrangement of syllables embedded within utterances and utterances embedded within prelinguistic phrases in the vocalizations of infants. Prelinguistic phrases were characterized by systematic lengthening of phrase final syllables, temporal patterning, and stable durations across development that were similar to those of some cross-culturally optimal rhythmic units from other domains. Analyses of vocalizations of infants with Down syndrome indicated similar internal structure of prelinguistic phrases to those of typically developing infants, but with longer durations. These findings suggest that relative durational characteristics of prelinguistic phrasing are stable features of early vocal behavior, although the absolute durational characteristics of prelinguistic phrases can be impacted by a complex and severe disorder such as Down syndrome.

Differential phonatory characteristics of four women with amyotrophic lateral sclerosis.

Patients with specific neural subsystem involvement are often reported to present with particular perceptual characteristics of voice. This has been true for diseases such as amyotrophic lateral sclerosis (ALS), a progressive disease in which mixed neurologic signs are present. This article reports acoustic data on the phonatory performance of four women diagnosed with ALS who had initial bulbar signs and progressive phonatory deterioration. The data presented here demonstrate that the phonatory characteristics of women with ALS are not uniform, but in fact may vary greatly from patient to patient.

Cross-language differences in phonological acquisition: Swedish and American /t/.

Our understanding of phonological acquisition has benefited immensely from cross-linguistic investigations which allow researchers to separate biological and learned factors. To date, most cross-linguistic studies have focused either on differences in phonetic inventories or on differences in frequency of occurrence of particular phonetic and phonological properties in the adult language. This paper describes a third type of study: comparisons of segments that occur in two (or more) languages but differ in their phonetic properties. We present perceptual and acoustic analyses of adult and child productions of word-initial alveolar /t/ in American English and dental /t/ in Swedish. Results showed that listeners' perception of place of articulation was strongly associated with language (alveolar: American English, dental: Swedish) for both adult and child tokens, and was effective in assigning individual speakers to language groups. Three acoustic measures, voice onset time, burst intensity and burst spectral diffuseness correlated with language for both child and adult tokens; the latter two measures correlated with perception as well. The findings suggest that American and Swedish children at 30 months of age have acquired some language-specific phonetic aspects of /t/ phonemes.

Speech analysis systems: an evaluation.

Performance characteristics are reviewed for seven systems marketed for acoustic speech analysis: CSpeech, CSRE, ILS-PC, Kay Elemetrics model 5500 Sona-Graph, MacSpeech Lab II, MSL, and Signalyze. The characteristics reviewed include system components, basic capabilities (signal acquisition, waveform operations, analysis, and other functions), documentation, user interface, data formats and journaling, speed and precision of spectral analysis, and speed and precision of fundamental frequency analysis. Basic capabilities are also tabulated for three recently introduced systems: the Sensimetrics SpeechStation, the Kay Elemetrics Computerized Speech Lab (CSL), and the LSI Speech Workstation. In addition to the capability and performance summaries, this article offers suggestions for continued development of speech analysis systems, particularly in data exchange, journaling, display features, spectral analysis, and fundamental frequency analysis.

Speech analysis systems: a survey.

Recently developed, relatively inexpensive systems make digital speech analysis available to many teachers, clinicians, and researchers who have not had access to previous systems. Addressing these prospective users, we survey five microcomputer programs and two dedicated devices for recording, editing, and analyzing speech. We review the capabilities, requirements, and user interface of each system. We recommend considerations for prospective users and for developers of the next generation of such programs and devices. Finally, we briefly survey seven additional systems.

The importance of the spin equilibrium in cytochrome P-450 for the reduction rate of the heme iron.

Based on the existence of a spin equilibrium of P-450 LM a thermodynamic model including the first two elementary steps has been developed. This model has been compared with a modified model of P-450 CAM first presented by SLIGAR [1]. For the quantitative description of the model of P-450 LM seven necessary constants have been calculated. In the model a 5-coordinated ferric heme complex as intermediate and precursor of the reduced state is included. The model is based on experimental data of the spin equilibrium and the binding of benzphetamine to P-450 LM2, on the redox potential of P-450 LM and further on the assumption of a structure of the precursor well adapted to reduction. The dissociation constant (KD) of the 6th heme iron ligand is calculated to be 0.03 meaning that only 3% of the high spin ferric state are 5-coordinated. From the thermodynamic parameters of the model the sequential order of the reaction process can be derived and conclusions can be drawn on possibly reaction controlling steps. Experimentally it is shown that the substrate induced spin shift is correlated with the reduction rate. This has been shown to be valid in dependence on the degree of saturation with only one substrate as well as with different substrates indicating that independent of the individual substrate only the shift of the spin state controls the reduction. From the experiments as well as from the model it can be concluded that P-450 works in the first reaction step in two states (different in structural and functional properties) being in equilibrium with each other. Different affinities of these two states towards the substrate shift the equilibrium. This shift increases the concentration of the reducible intermediate and by this the reduction as second elementary step is regulated.

Study of DNA-spermine interactions by use of small-angle and wide-angle X-ray scattering and circular dichroism.

Circular dichroism measurements with DNA-spermine complexes at 0.075 M NaCl and at 0.15 M NaCl reveal +psi (type I) and -psi (type II) CD spectra respectively. From small-angle X-ray scattering studies it could be shown that type I has a long-range order, short-range order supramolecular structure, while type II is of long-range disorder, short-range disorder structure. The secondary structure of the DNA in both types of condensates is B-like as concluded from wide-angle X-ray scattering diagrams of the condensates and from a comparison with the wide-angle X-ray curves of DNA and RNA in solution.

[Secondary structure of condensed DNA. wide-angle, small-angle x-ray scattering and circular dichroism]. / Sekundärstruktur kondensierter DNS. Vergleichende Untersuchungen der diffusen Röntgen-Weitwinkelstreuung und des Zirkulardichroismus.

Ethanol precipitated DNA shows a CD spectrum of the +psi-type which is similar to that of DNA in the A-form. DNA condensed with cetyl-trimethylammonium-bromide shows, depending on the condensation velocity, a CD spectrum of the -psi-type, or a CD spectrum only slightly modified from that of DNA in solution. The first spectrum is similar to that of DNA in the C-form, and the second one, to that of DNA in the B-form. Using large-angle X-ray scattering of the three DNA condensates and comparing them with the scattering curves calculated from the atom coordinates for the A-, B-, and C-form of DNA it is shown that the secondary structure of the DNA belongs in all three cases to the B-family. It follows from this result that the secondary structure of DNA alone does not determine the type of CD spectrum. The CD spectrum of condensed DNA is essentially determined by the supramolecular structures of the partially crystalline DNA condensates. These supramolecular structures can be demonstrated by the small-angle X-ray diagrams. The condensation of DNA by ethanol and cetyl-trimethylammonium-bromide proceeds in the form of a partial crystallization of the DNA.

Substrate binding to solubilized cytochrome P-450 from rabbits at different temperatures.

The binding affinities of selected type I- and type II-substrates to partially purified cytochrome p-450 from rabbit liver microsomes were studied and found to differ from those of rats. The temperature dependence of the apparent binding constants qualitatively exhibited the same characteristics compared with that of rats. For type I-substrates endothermic and for type II-substrates exothermic reaction characteristics were observed. Taking into account the partition coefficients of the substrates so far investigated it is obvious that type I substrates with increasing hydrophobicity are bound more strongly while type II-substrates show a more complicated behvaiour. This may due to the fact that other types of binding are included besides the hydrophobic interactions.

Differentiation between type I and type II substrate binding to cytochrome P-450 by variation of temperature.

The binding affinities of type I- and type II-substrates to cytochrome P-450 solubilized from phenobarbital induced rat liver microsomes in dependence on the temperature have been determined. Both classes of substrates have been found to exhibit different temperature behaviour. The tendency of type I-substrates (benzphetamine and hexobarbital) to form complexes increases with increasing temperature; type II-substrates show the inverse tendency. From the van't Hoff plot the binding enthalpy was calculated and discussed in connection with the entropy and free enthalpy values. These data ascertain the suggestion of different binding sites for both classes of substrates.

Folding crystallization of DNA. Circular dichroism studies.

CD spectra of DNA monocrystals are extremely different from spectra of psi-DNA or DNA-histone H1 or DNA-polylysine complexes. They are discussed to be dependent on the supramolecular organization of DNA in the condensed form, and they are not in contradiction to the previously proposed seven folding model of DNA in chromatin. Conclusions are drawn with regard to the interpretation of chromatin CD spectra.

Circular dichroism studies on DNA condensed in NaCl cetyltrimethyl ammonium bromide solutions.

It is shown by means of circular dichroism studies of variously condensed forms of DNA that the specific supramolecular structure of DNA determines the type of CD spectra. DNA, condensed (crystallized) slowly in the presence of cetyltrimethyl ammonium bromide yields a spectrum very similar to that of DNA in solution in the B-form. The condensates appear in the phase-contrast microscope as spherulitic crystallites. Rapidly condensed DNA in the presence of cetyltrimethyl ammonium bromide shows a spectrum of the psi-type with large negative ellipticites. The influence of condensation velocity upon the supramolecular structure of DNA gives evidence that the various condensation forms of DNA are not thermodynamical equilibrium conformations.

[Interaction of substrate with cytochrome P-450 in microsomal and solubilized form]. / Wechselwirkung von Substraten mit Zytochrom P-450 in mikrosomaler und solubilisierter Form

In order to characterize the substrate binding sites, difference spectroscopic titrations in microsomal and solubilized cytochrome P-450 from induced and non-induced rat liver microsomes were performed. The binding constants determined show differences depending on the physicochemical nature of the substrate and the degree of integration of the enzyme system. In hydrophilic substrates the differences of the binding to the microsomal or solubilized form are less pronounced than in lipophilic ones. From the comparison of the parameters obtained at various levels of integration it is concluded that the micromilieu of the binding site is of great importance for the binding of the substrate of cytochrome P-450.