387 research outputs found

    Assessing the Prosody of Non-Native Speakers of English: Measures and Feature Sets

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    In this paper, we describe a new database with audio recordings of non-native (L2) speakers of English, and the perceptual evaluation experiment conducted with native English speakers for assessing the prosody of each recording. These annotations are then used to compute the gold standard using different methods, and a series of regression experiments is conducted to evaluate their impact on the performance of a regression model predicting the degree of Abstract naturalness of L2 speech. Further, we compare the relevance of different feature groups modelling prosody in general (without speech tempo), speech rate and pauses modelling speech tempo (fluency), voice quality, and a variety of spectral features. We also discuss the impact of various fusion strategies on performance.Overall, our results demonstrate that the prosody of non-native speakers of English as L2 can be reliably assessed using supra- segmental audio features; prosodic features seem to be the most important ones

    Phonetic and prosodic analysis of speech

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    In order to cope with the problems of spontaneous speech (including, for example, hesitations and non-words) it is necessary to extract from the speech signal all information it contains. Modeling of words by segmental units should be supported by suprasegmental units since valuable information is represented in the prosody of an utterance. We present an approach to flexible and efficient modeling of speech by segmental units and describe extraction and use of suprasegmental information

    Improving parsing of spontaneous speech with the help of prosodic boundaries

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    Parsing can be improved in automatic speech understanding if prosodic boundary marking is taken into account, because syntactic boundaries are often marked by prosodic means. Because large databases are needed for the training of statistical models for prosodic boundaries, we developed a labeling scheme for syntactic-prosodic boundaries within the German VERBMOBIL project (automatic speech-to-speech translation). We compare the results of classifiers (multi-layer perceptrons and language models) trained on these syntactic-prosodic boundary labels with classifiers trained on perceptual-prosodic and purely syntactic labels. Recognition rates of up to 96% were achieved. The turns that we need to parse consist of 20 words on the average and frequently contain sequences of partial sentence equivalents due to restarts, ellipsis, etc. For this material, the boundary scores computed by our classifiers can successfully be integrated into the syntactic parsing of word graphs; currently, they improve the parse time by 92% and reduce the number of parse trees by 96%. This is achieved by introducing a special Prosodic Syntactic Clause Boundary symbol (PSCB) into our grammar and guiding the search for the best word chain with the prosodic boundary scores

    Major biological obstacles for persistent cell-based regeneration of articular cartilage

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    Hyaline articular cartilage, the load-bearing tissue of the joint, has very limited repair and regeneration capacities. The lack of efficient treatment modalities for large chondral defects has motivated attempts to engineer cartilage constructs in vitro by combining cells, scaffold materials and environmental factors, including growth factors, signaling molecules, and physical influences. Despite promising experimental approaches, however, none of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The reasons for this are diverse and can ultimately result in matrix degradation, differentiation or integration insufficiencies, or loss of the transplanted cells and tissues. This article aims to systematically review the different causes that lead to these impairments, including the lack of appropriate differentiation factors, hypertrophy, senescence, apoptosis, necrosis, inflammation, and mechanical stress. The current conceptual basis of the major biological obstacles for persistent cell-based regeneration of articular cartilage is discussed, as well as future trends to overcome these limitations

    Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head

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    Avascular necrosis (AVN) of the femoral head is a debilitating disease of multifactorial genesis, predominately affects young patients, and often leads to the development of secondary osteoarthritis. The evolving field of regenerative medicine offers promising treatment strategies using cells, biomaterial scaffolds, and bioactive factors, which might improve clinical outcome. Early stages of AVN with preserved structural integrity of the subchondral plate are accessible to retrograde surgical procedures, such as core decompression to reduce the intraosseous pressure and to induce bone remodeling. The additive application of concentrated bone marrow aspirates, ex vivo expanded mesenchymal stem cells, and osteogenic or angiogenic growth factors (or both) holds great potential to improve bone regeneration. In contrast, advanced stages of AVN with collapsed subchondral bone require an osteochondral reconstruction to preserve the physiological joint function. Analogously to strategies for osteochondral reconstruction in the knee, anterograde surgical techniques, such as osteochondral transplantation (mosaicplasty), matrix-based autologous chondrocyte implantation, or the use of acellular scaffolds alone, might preserve joint function and reduce the need for hip replacement. This review summarizes recent experimental accomplishments and initial clinical findings in the field of regenerative medicine which apply cells, growth factors, and matrices to address the clinical problem of AVN. © 2012 BioMed Central Ltd

    A Potent and Selective Inhibitor of Cdc42 GTPase

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    Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). Given the highly complementary nature of the function of the Rho family GTPases, Cdc42 selective inhibitors such as those reported here should help untangle the roles of the proteins in this family

    Lady Gaga as (dis)simulacrum of monstrosity

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    Lady Gaga’s celebrity DNA revolves around the notion of monstrosity, an extensively researched concept in postmodern cultural studies. The analysis that is offered in this paper is largely informed by Deleuze and Guattari’s notion of monstrosity, as well as by their approach to the study of sign-systems that was deployed in A Thousand Plateaus. By drawing on biographical and archival visual data, with a focus on the relatively underexplored live show, an elucidation is afforded of what is really monstrous about Lady Gaga. The main argument put forward is that monstrosity as sign seeks to appropriate the horizon of unlimited semiosis as radical alterity and openness to signifying possibilities. In this context it is held that Gaga effectively delimits her unique semioscape; however, any claims to monstrosity are undercut by the inherent limits of a representationalist approach in sufficiently engulfing this concept. Gaga is monstrous for her community insofar as she demands of her fans to project their semiosic horizon onto her as a simulacrum of infinite semiosis. However, this simulacrum may only be evinced in a feigned manner as a (dis)simulacrum. The analysis of imagery from seminal live shows during 2011–2012 shows that Gaga’s presumed monstrosity is more akin to hyperdifferentiation as simultaneous employment of heterogeneous and potentially dissonant inter pares cultural representations. The article concludes with a problematisation of audience effects in the light of Gaga’s adoption of a schematic and post-representationalist strategy in the event of her strategy’s emulation by competitive artists

    Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe

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    Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochemical characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and molecular pathway studies that involve GTPases.This work was supported by National Science Foundation (NSF) Grant MCB0956027 and National Institutes of Health Grant R03 MH081231-01 from the Molecular Libraries Program (to A. W. N.); University of New Mexico Center for Molecular Discovery Molecular Libraries Probe Production Centers (UNMCMD MLPCN) National Institutes of Health Grants U54MH084690 and R01HL081062 (to L. A. S.); UNM National Center for Research Resources (NCRR) Grant 5P20RR016480 (to L. G. H.); National Institutes of Health Grant R21 CA170375-01 through the NCI (to A. W. N., L. G. H., and J. E. G.); National Institutes of Health Grants NS066429 and AI092130 (to T. B.); and University of Kansas Specialized Chemistry Center (KUSCC) MLPCN National Institutes of Health Grant U54HG005031 (to J. A.)
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