26 research outputs found

    Monolingual and crosslingual comparison of tandem features derived from articulatory and phone MLPs

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    In recent years, the features derived from posteriors of a multilayer perceptron (MLP), known as tandem features, have proven to be very effective for automatic speech recognition. Most tandem features to date have relied on MLPs trained for phone classification. We recently showed on a relatively small data set that MLPs trained for articulatory feature classification can be equally effective. In this paper, we provide a similar comparison using MLPs trained on a much larger data set - 2000 hours of English conversational telephone speech. We also explore how portable phone- and articulatory feature- based tandem features are in an entirely different language - Mandarin - without any retraining. We find that while phone-based features perform slightly better in the matched-language condition, they perform significantly better in the cross-language condition. Yet, in the cross-language condition, neither approach is as effective as the tandem features extracted from an MLP trained on a relatively small amount of in-domain data. Beyond feature concatenation, we also explore novel observation modelling schemes that allow for greater flexibility in combining the tandem and standard features at hidden Markov model (HMM) outputs

    ORALLY ACTIVE INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. II. DISPOSITION OF L-694,458 IN RATS AND RHESUS MONKEYS

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    ABSTRACT: The disposition of L-694,458, a potent monocyclic ␀-lactam inhibitor of human leukocyte elastase, was studied in male SpragueDawley rats and rhesus monkeys. After iv dosing, L-694,458 exhibited similar pharmacokinetic parameters in rats and rhesus monkeys. The mean values for its plasma clearance, terminal halflife, and volume of distribution at steady state were 27 ml/min/kg, 1.8 hr, and 4.0 liters/kg in rats and 34 ml/min/kg, 2.3 hr, and 5 liters/kg in rhesus monkeys. The bioavailability of a 10 mg/kg oral dose was higher in rats (65%) than in rhesus monkeys (39%). In both species, concentrations of L-694,458 in plasma increased more than proportionally when the oral dose was increased from 10 mg/kg to 40 mg/kg. In monkeys a protracted plasma concentration-time profile was observed at 40 mg/kg, characterized by a delayed T max (8-24 hr) and a long terminal half-life (6 hr). [ 3 H]L-694,458 was well absorbed after oral dosing to rats at 10 mg/kg, as indicated by the high recovery of radioactivity in bile (83%) and urine (6%) of bile duct-cannulated rats. Only Ïł5% or less of the radioactivity in bile, urine, and feces was a result of intact L-694,458, indicating that the compound was being eliminated by metabolism, followed by excretion of the metabolites in feces, via bile. Demethylenation of the methylenedioxyphenyl group resulting in the catechol was the primary metabolic pathway in human and rhesus monkey liver microsomes. In rat liver microsomes, the major metabolite was the N-oxide of the methyl-substituted piperazine nitrogen. In rats dosed iv and orally with [ 3 H]L-694,458, concentrations of radioactivity were highest in the lung (the primary target tissue), adrenals, and liver. L-694,458 was unstable in rat blood and plasma, degrading via a pathway believed to be catalyzed by B-esterases and to involve cleavage of the ␀-lactam ring and loss of the methylpiperazine phenoxy group. In vitro studies indicated that in human liver, L-694,458 was metabolized by CYP3A and 2C isozymes, and in both monkey and human liver microsomes the compound acted as an inhibitor of testosterone 6␀-hydroxylation. Leukocyte elastase is a serine protease capable of proteolytic degradation of a variety of substrates, including elastin and collagen, which are components of connective tissue. Specific inhibitors of leukocyte elastase are being explored as potential therapeutic agents for the treatment of inflammatory diseases, such as cystic fibrosis and rheumatoid arthritis where high amounts of extracellular elastase, either free or bound to its natural inhibitors, ␣ 1 -proteinase inhibitor and secretory leukocyte proteinase inhibitor, have been detected extracellularly (1-3). Several classes of inhibitors of elastase have been synthesized and evaluated to date (4 -19). L-694,458 Materials and Methods Chemicals. L-694,458 ( Microsomes. Fresh rat liver and frozen human and rhesus monkey liver tissue were used for the preparation of microsomes. Microsomes containing 1 Abbreviations used are: L-694,458, N-[1(R)-(1,3-benzodioxol-5-yl

    Articulatory feature-based methods for acoustic and audio-visual speech recognition: Summary from the 2006 JHU Summer Workshop.

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    We report on investigations, conducted at the 2006 Johns HopkinsWorkshop, into the use of articulatory features (AFs) for observation and pronunciation models in speech recognition. In the area of observation modeling, we use the outputs of AF classiers both directly, in an extension of hybrid HMM/neural network models, and as part of the observation vector, an extension of the tandem approach. In the area of pronunciation modeling, we investigate a model having multiple streams of AF states with soft synchrony constraints, for both audio-only and audio-visual recognition. The models are implemented as dynamic Bayesian networks, and tested on tasks from the Small-Vocabulary Switchboard (SVitchboard) corpus and the CUAVE audio-visual digits corpus. Finally, we analyze AF classication and forced alignment using a newly collected set of feature-level manual transcriptions

    MONOLINGUAL AND CROSSLINGUAL COMPARISON OF TANDEM FEATURES DERIVED FROM ARTICULATORY AND PHONE MLPS

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    In recent years, the features derived from posteriors of a multilayer perceptron (MLP), known as tandem features, have proven to be very effective for automatic speech recognition. Most tandem features to date have relied on MLPs trained for phone classification. We recently showed on a relatively small data set that MLPs trained for articulatory feature classification can be equally effective. In this paper, we provide a similar comparison using MLPs trained on a much larger data set—2000 hours of English conversational telephone speech. We also explore how portable phone- and articulatory featurebased tandem features are in an entirely different language— Mandarin—without any retraining. We find that while the phone-based features perform slightly better in the matchedlanguage condition, they perform significantly better in the cross-language condition. Yet, in the cross-language condition, neither approach is as effective as the tandem features extracted from an MLP trained on a relatively small amount of in-domain data. Beyond feature concatenation, we also explore novel observation modeling schemes that allow for greater flexibility in combining the tandem and standard features at hidden Markov model (HMM) outputs. Index Terms — Speech recognition, feedforward neural networks, hidden Markov models

    Characterisation of alleles of tomato light signalling genes generated by TILLING

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    Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699International audienceTargeting Induced Local Lesions IN Genomes (TILLING) combines chemical mutagenesis with high throughput screening to allow the generation of alleles of selected genes. In this study, TILLING has been applied to produce a series of mutations in genes encoding essential components of the tomato light signal transduction pathway in an attempt to enhance fruit nutritional quality. Point mutations to DEETIO-LATED1 (DET1), which is responsible for the high pigment2 (hp2) tomato mutant, resulted in elevated levels of both carotenoid and phenylpropanoid phytonutrients in ripe fruit, whilst immature fruit showed increased chlorophyll content, photosynthetic capacity and altered fruit morphology. Furthermore, genotypes with mutations to the UV-DAMAGED DNA BINDING PROTEIN 1 (DDB1), COP1 and COP1 like were also characterised. These genotypes largely did not display phenotypes characteristic of mutation to light signalling components but their characterisation has enabled interrogation of structure function relationships of the mutated genes. (C) 2012 Elsevier Ltd. All rights reserved

    Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism

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    Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws(1) followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.Harvard Univ, Sch Med, Harvard Forsyth Dept Oral Biol, Harvard Sch Dent Med, Boston, MA USAHarvard Univ, Sch Med, Forsyth Inst, Boston, MA USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA USAUniversidade Federal de SĂŁo Paulo, EPM, Campinas, SP, BrazilSOBRAPAR, Inst Cirug Plast Craniofacial, Campinas, SP, BrazilHumboldt Univ, Inst Med Genet, Sch Med, Berlin, GermanyTampa Craniofacial Ctr, Tampa, FL USAUniv Calif Davis, Sacramento, CA 95817 USASo Maine Oral & Maxillofacial Surg, S Portland, ME USAUniv Copenhagen, Sch Dent, Dept Pediat Dent, Copenhagen, DenmarkUniversidade Federal de SĂŁo Paulo, EPM, Campinas, SP, BrazilWeb of Scienc
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