Uses of the pitch-scaled harmonic filter in speech processing

The pitch-scaled harmonic filter (PSHF) is a technique for decomposing speech signals into their periodic and aperiodic constituents, during periods of phonation. In this paper, the use of the PSHF for speech analysis and processing tasks is described. The periodic component can be used as an estimate of the part attributable to voicing, and the aperiodic component can act as an estimate of that attributable to turbulence noise, i.e., from fricative, aspiration and plosive sources. Here we present the algorithm for separating the periodic and aperiodic components from the pitch-scaled Fourier transform of a short section of speech, and show how to derive signals suitable for time-series analysis and for spectral analysis. These components can then be processed in a manner appropriate to their source type, for instance, extracting zeros as well as poles from the aperiodic spectral envelope. A summary of tests on synthetic speech-like signals demonstrates the robustness of the PSHF's performance to perturbations from additive noise, jitter and shimmer. Examples are given of speech analysed in various ways: power spectrum, short-time power and short-time harmonics-to-noise ratio, linear prediction and mel-frequency cepstral coefficients. Besides being valuable for speech production and perception studies, the latter two analyses show potential for incorporation into speech coding and speech recognition systems. Further uses of the PSHF are revealing normally-obscured acoustic features, exploring interactions of turbulence-noise sources with voicing, and pre-processing speech to enhance subsequent operations

Potent Trivalent Inhibitors of Thrombin through Hybridization of Salivary Sulfopeptides from Hematophagous Arthropods

Blood feeding arthropods, such as leeches, ticks, flies and mosquitoes, provide a privileged source of peptidic anticoagulant molecules. These primarily operate through inhibition of the central coagulation protease thrombin by binding to the active site and either exosite I or exosite II. Herein, we describe the rational design of a novel class of trivalent thrombin inhibitors that simultaneously block both exosites as well as the active site. These engineered hybrids were synthesized using tandem diselenide-selenoester ligation (DSL) and native chemical ligation (NCL) reactions in one-pot. The most potent trivalent inhibitors possessed femtomolar inhibition constants against alpha-thrombin and were selective over related coagulation proteases. A lead hybrid inhibitor possessed potent anticoagulant activity, blockade of both thrombin generation and platelet aggregation in vitro and efficacy in a murine thrombosis model at 1 mg kg(-1). The rational engineering approach described here lays the foundation for the development of potent and selective inhibitors for a range of other enzymatic targets that possess multiple sites for the disruption of protein-protein interactions, in addition to an active site

Analysis of mixed-source speech sounds: aspiration, voiced fricatives and breathiness

Our initial goal was to model the source characteristics of aspiration more accurately. The term is used inconsistently in the literature, but there is general agreement that aspiration is produced by turbulence noise generated in the vicinity of the glottis. Thus, in order to model aspiration, we must refine its concept, and in particular define its relation to other kinds of noise produced near the glottis, such as breathiness and hoarseness. For instance, do similar aeroacoustic processes operate transiently during a plosive release and steadily during a breathy vowel? In unvoiced fricatives, localized sources produce well-defined spectral troughs. We have therefore developed a series of analysis methods that generate spectra for transient and voice-and-noise-excited sounds. These methods include pitch-synchronous decomposition into harmonic and anharmonic components (based on a hoarseness metric of Muta et al., 1988), short-time spectra, ensemble averaging, and short-time harmonics-to-noise ratios (Jackson and Shadle, 1998). These have been applied to a corpus of repeated nonsense words consisting of aspirated stops in three vowel contexts and voiced and unvoiced fricatives, spoken in four voice qualities, thus providing multiple examples of mixed-source and transient-source speech sounds. Ensemble-averaged spectra derived throughout a stop release show evidence of a highly-localized noise source becoming more distributed. Variations by place are also apparent, complementing and extending previous work (Stevens and Blumstein, 1978; Stevens, 1993). The coordination of glottal and supraglottal articulation, described and modelled for aspiration by Scully and Mair (1995), is in a sense reversed for voiced fricatives. Use of the decomposition algorithm on voiced fricatives revealed greater complexity than expected: the anharmonic component appears sometimes to be modulated by the harmonic component, sometimes to be independent of it, and tends to change from one case to the other in the course of the fricative. In sum, we have made some progress in describing not only spectral but time-varying properties of an aspiration model, and in so doing, have improved our descriptions of other mixed-source, time-varying speech sounds