Implementation and Evaluation of Acoustic Distance Measures for Syllables

Munier C. Implementation and Evaluation of Acoustic Distance Measures for Syllables. Bielefeld (Germany): Bielefeld University; 2011.In dieser Arbeit werden verschiedene akustische Ähnlichkeitsmaße für Silben motiviert und anschließend evaluiert. Der Mahalanobisabstand als lokales Abstandsmaß für einen Dynamic-Time-Warping-Ansatz zum Messen von akustischen Abständen hat die Fähigkeit, Silben zu unterscheiden. Als solcher erlaubt er die Klassifizierung von Silben mit einer Genauigkeit, die für die Klassifizierung von kleinen akustischen Einheiten üblich ist (60 Prozent für eine Nächster-Nachbar-Klassifizierung auf einem Satz von zehn Silben für Samples eines einzelnen Sprechers). Dieses Maß kann durch verschiedene Techniken verbessert werden, die jedoch seine Ausführungsgeschwindigkeit verschlechtern (Benutzen von mehr Mischverteilungskomponenten für die Schätzung von Kovarianzen auf einer Gaußschen Mischverteilung, Benutzen von voll besetzten Kovarianzmatrizen anstelle von diagonalen Kovarianzmatrizen). Durch experimentelle Evaluierung wird deutlich, dass ein gut funktionierender Algorithmus zur Silbensegmentierung, welcher eine akkurate Schätzung von Silbengrenzen erlaubt, für die korrekte Berechnung von akustischen Abständen durch die in dieser Arbeit entwickelten Ähnlichkeitsmaße unabdingbar ist. Weitere Ansätze für Ähnlichkeitsmaße, die durch ihre Anwendung in der Timbre-Klassifizierung von Musikstücken motiviert sind, zeigen keine adäquate Fähigkeit zur Silbenunterscheidung.In this work, several acoustic similarity measures for syllables are motivated and successively evaluated. The Mahalanobis distance as local distance measure for a dynamic time warping approach to measure acoustic distances is a measure that is able to discriminate syllables and thus allows for syllable classification with an accuracy that is common to the classification of small acoustic units (60 percent for a nearest neighbor classification of a set of ten syllables using samples of a single speaker). This measure can be improved using several techniques that however impair the execution speed of the distance measure (usage of more mixture density components for the estimation of covariances from a Gaussian mixture model, usage of fully occupied covariance matrices instead of diagonal covariance matrices). Through experimental evaluation it becomes evident that a decently working syllable segmentation algorithm allowing for accurate syllable border estimations is essential to the correct computation of acoustic distances by the similarity measures developed in this work. Further approaches for similarity measures which are motivated by their usage in timbre classification of music pieces do not show adequate syllable discrimination abilities

Comparison of phenolic and volatile profiles of edible and toxic forms of Detarium senegalense J. F. GMEL

In Senegal, Detarium senegalense J.F. Gmel. (ditax in Wolof) is one of the most important important forest fruit species. However, exploitation of the edible fruit is based on local people's knowledge. Only trees whose fruits are consumed by animals are exploited. To identify them, a chemical comparison of edible and toxic forms was done in order to highlight differences between both forms. Dichloromethane leaf extracts from toxic and edible trees were analyzed by gas chromatography. Phenolic profile and volatile compounds from fruits extracts were studied respectively by High Performance Liquid Chromatography-mass spectrometry (HPLC-MS) and Gas Chromatography Mass Spectrometry (GC-MS). Cytotoxicity effect of fruits extracts was evaluated on murine macrophage cells J774 A1. GC-analysis of dichloromethane leaf extracts revealed the presence of lupenone and lupeol only in toxic extracts. 6'-O-galloyl-epiheterodendrin and isovaleronitrile were detected in toxic pulp. However, no cytotoxic effect was found in our conditions. This study has given the opportunity to identify within the same species, compounds which could differentiate both edible and toxic forms. Nevertheless further studies are needed to better understand which compounds are responsible for toxicity in the toxic form. (Résumé d'auteur

Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators

The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein-protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. However, the specific phosphorylation sites on the GR that trigger these interactions and their functional consequences are less clear. Hence, we sought to examine this system in more detail. We used phosphorylated GR peptides, biophysical studies, and X-ray crystallography to identify key residues within the ligand-binding domain of the GR, T524 and S617, whose phosphorylation results in binding of the representative 14-3-3 protein 14-3-3ζ. A kinase screen identified misshapen-like kinase 1 (MINK1) as responsible for phosphorylating T524 and Rho-associated protein kinase 1 for phosphorylating S617; cell-based approaches confirmed the importance of both GR phosphosites and MINK1 but not Rhoassociated protein kinase 1 alone in inducing GR-14-3-3 binding. Together our results provide molecular-level insight into 14-3-3-mediated regulation of the GR and highlight both MINK1 and the GR-14-3-3 axis as potential targets for future therapeutic intervention

Belatacept and long-term outcomes in kidney transplantation

Background: in previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. Methods: we randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). Results: a total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. Conclusions: seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750)

Leber Congenital Amaurosis: Comprehensive Survey of the Genetic Heterogeneity, Refinement of the Clinical Definition, and Genotype-Phenotype Correlations as a Strategy for Molecular Diagnosis

Communicated by Jean-Claude Kaplan Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium but they are involved in strikingly different physiologic pathways resulting in an unforeseeable physiopathologic variety. This wide genetic and physiologic heterogeneity that could largely increase in the coming years, hinders the molecular diagnosis in LCA patients. The genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here, we report a comprehensive mutational analysis of the all known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% patients. GUCY2D appeared to account for most LCA cases of our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%), and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited to search for phenotype variations. Sound genotype-phenotype correlations were found that allowed us to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rodcone dystrophy. Besides, objective ophthalmologic data allowed us to subdivide each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the heavy task of genotyping new patients but only if one has access to the most precise clinical history since birth

Acoustic Packaging and the Learning of Words

Schillingmann L, Wagner P, Munier C, Wrede B, Rohlfing K. Acoustic Packaging and the Learning of Words. Presented at the IEEE ICDL-EPIROB 2011 (1st Joint IEEE International Conference on Development and Learning and on Epigenetic Robotics), Frankfurt, Germany

Using Prominence Detection to Generate Acoustic Feedback in Tutoring Scenarios

Schillingmann L, Wagner P, Munier C, Wrede B, Rohlfing K. Using Prominence Detection to Generate Acoustic Feedback in Tutoring Scenarios. In: Interspeech 2011 (12th Annual Conference of the International Speech Communication Association). 2011: 3105-3108.Robots interacting with humans need to understand actions and make use of language in social interactions. Research on infant development has shown that language helps the learner to structure visual observations of action. This acoustic information typically in the form of narration overlaps with action sequences and provides infants with a bottom-up guide to find structure within them. This concept has been introduced as acoustic packaging by Hirsh-Pasek and Golinkoff. We developed and integrated a prominence detection module in our acoustic packaging system to detect semantically relevant information linguistically highlighted by the tutor. Evaluation results on speech data from adult-infant interactions show a significant agreement with human raters. Furthermore a first approach based on acoustic packages which uses the prominence detection results to generate acoustic feedback is presented. Index Terms: prominence, multimodal action segmentation, human robot interaction, feedbac

14-3-3 modulation of the inflammatory response

Regulation of inflammation is a central part of the maintenance of homeostasis by the immune system. One important class of regulatory protein that has been shown to have effects on the inflammatory process are the 14−3-3 proteins. Herein we describe the roles that have been identified for 14−3-3 in regulation of the inflammatory response. These roles encompass regulation of the response that affect inflammation at the genetic, molecular and cellular levels. At a genetic level 14−3-3 is involved in the regulation of multiple transcription factors and affects the transcription of key effectors of the immune response. At a molecular level many of the constituent parts of the inflammatory process, such as pattern recognition receptors, protease activated receptors and cytokines are regulated through phosphorylation and recognition by 14−3-3 whilst disruption of the recognition processes has been observed to result in clinical syndromes. 14−3-3 is also involved in the regulation of cell proliferation and differentiation, this has been shown to affect the immune system, particularly T- and B-cells. Finally, we discuss how abnormal levels of 14−3-3 contribute to undesirable immune responses and chronic inflammatory conditions