Voicing quantification is more relevant than period perturbation in substitution voices: an advanced acoustical study

Quality of substitution voicing—i.e., phonation with a voice that is not generated by the vibration of two vocal folds—cannot be adequately evaluated with routinely used software for acoustic voice analysis that is aimed at ‘common’ dysphonias and nearly periodic voice signals. The AMPEX analysis program (Van Immerseel and Martens) has been shown previously to be able to detect periodicity in irregular signals with background noise, and to be suited for running speech. The validity of this analysis program is first tested using realistic synthesized voice signals with known levels of cycle-to-cycle perturbations and additive noise. Second, exhaustive acoustic analysis is performed of the voices of 116 patients surgically treated for advanced laryngeal cancer and recorded in seven European academic centers. All of them read out a short phonetically balanced passage. Patients were divided into six groups according to the oscillating structures they used to phonate. Results show that features related to quantification of voicing enable a distinction between the different groups, while the features reporting F0-instability fail to do so. Acoustic evaluation of voice quality in substitution voices thus best relies upon voicing quantification

Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP

Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK modul

Ligand Binding Study of Human PEBP1/RKIP: Interaction with Nucleotides and Raf-1 Peptides Evidenced by NMR and Mass Spectrometry

Background Human Phosphatidylethanolamine binding protein 1 (hPEBP1) also known as Raf kinase inhibitory protein (RKIP), affects various cellular processes, and is implicated in metastasis formation and Alzheimer's disease. Human PEBP1 has also been shown to inhibit the Raf/MEK/ERK pathway. Numerous reports concern various mammalian PEBP1 binding ligands. However, since PEBP1 proteins from many different species were investigated, drawing general conclusions regarding human PEBP1 binding properties is rather difficult. Moreover, the binding site of Raf-1 on hPEBP1 is still unknown. Methods/Findings In the present study, we investigated human PEBP1 by NMR to determine the binding site of four different ligands: GTP, FMN, and one Raf-1 peptide in tri-phosphorylated and non-phosphorylated forms. The study was carried out by NMR in near physiological conditions, allowing for the identification of the binding site and the determination of the affinity constants KD for different ligands. Native mass spectrometry was used as an alternative method for measuring KD values. Conclusions/Significance Our study demonstrates and/or confirms the binding of hPEBP1 to the four studied ligands. All of them bind to the same region centered on the conserved ligand-binding pocket of hPEBP1. Although the affinities for GTP and FMN decrease as pH, salt concentration and temperature increase from pH 6.5/NaCl 0 mM/20°C to pH 7.5/NaCl 100 mM/30°C, both ligands clearly do bind under conditions similar to what is found in cells regarding pH, salt concentration and temperature. In addition, our work confirms that residues in the vicinity of the pocket rather than those within the pocket seem to be required for interaction with Raf-1.METASU

ICAR: endoscopic skull‐base surgery

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Evaluation of surgical treatment outcome in real-time conditions using a portable device :preliminary data

info:eu-repo/semantics/publishe

To what degree of voice perturbation are jitter measurements valid? A novel approach with synthesized vowels and visuo-perceptual pattern recognition

Objective measurement of the severity of dysphonia typically requires signal processing algorithms applied to acoustic recordings. Since Lieberman (1963) introduced the concept of perturbation analysis in the area of voice, the best-known acoustic parameter in clinical practice is conventional jitter. However, jitter measurements have some critical limitations. According to a widely accepted guideline, in sustained vowels of dysphonic voices, only perturbation measures less than about 5% are reliable: this is related to period extraction methods. This limit of 5% deserves critical analysis, certainly when there are indications that some acoustic analysis programs can be applied to quite irregular voices such as substitution voices. The present experiment demonstrates that - on signals of synthesized deviant voices (sustained vowel) with moderate additive noise - different raters are able to visually identify in a very consistent way the period durations of successive cycles up to values of about 13% jitter. Furthermore, even for higher values - over 30% - the jitter % computed with the period values rated by visual perception is, for some of the raters, very comparable to the real value. This suggests that improved acoustic programs using more reliable algorithms could validly transgress the traditional limit of 5% if they demonstrate the correspondence of their computations with the true jitter values. This is now made possible by synthesizers generating artificial deviant voices that cannot be distinguished from true dysphonia, and in which the jitter put in is exactly known. © 2011 Elsevier Ltd. All rights reserved.SCOPUS: cp.jinfo:eu-repo/semantics/publishe