Production and perception of Korean and English word-level prominence by Korean speakers

Prominence refers to the relative emphasis that may be given to a syllable in a word (word-level prominence) or to one or more words in a phrase (phrase-level prominence). Korean has been claimed to have both word-level (Ko, 2013) and phrase-level (Jun, 1996) prominence, with the former realized mainly with duration and the latter with F0 height. However, given the claim that younger Korean speakers have lost duration as the main cue expressing word-level prominence (Kim & Han, 1998; Magen & Blumstein, 1993), it is not clear if and how younger Korean speakers produce word-level prominence. Thus, the primary goal of the current dissertation is to examine whether Korean still has word-level prominence. Two experiments investigated this research question in two domains – acoustically (Experiment 1) and perceptually (Experiment 2). Given the findings regarding the status of lexical stress in Korean, we further investigated which acoustic correlates/cues Korean learners of English are able to transfer from their L1 prosodic cues, and whether they can acquire a new cue that does not exist in their L1. Thus, the secondary purpose of this study is to investigate which acoustic correlates/cues Korean L2 learners of English utilize in producing and perceiving English lexical stress. These questions are addressed and examined in Experiments 3 and 4. In the acoustic study of the production of Korean word-level prominence (Experiment 1), measurements of duration, intensity, F0, F1, and F2 on (so-called) Korean stress minimal pairs by older and younger Korean speakers revealed that only at the sentence level, duration and intensity systematically distinguish stress pairs for the older speakers. A perception study on word-level prominence in Korean (Experiment 2) revealed that both older and younger Korean listeners weighted the duration cue most heavily in identifying minimal pairs of Korean word-level prominence when two of the suprasegmental cues were orthogonally manipulated in each syllable. Interestingly, this perceptual weighting was only observed in the first syllable: none of the listeners changed their perception when cues were signaling second-syllable stress. Based on these findings from an acoustic and a perception study, we conclude that Korean does not have word-level prominence, but only has a phonemic vowel length distinction. In the acoustic study on the production of English word-level prominence (Experiment 3), measurements of duration, intensity, F0, F1, and F2 on English stress pairs found that Korean learners were able to use not only all suprasegmental cues to indicate lexical stress in English, but also acquire a new cue (e.g., vowel reduction) that does not exist in their native language, although in a non-native like manner. The results of the perception study on word-level prominence in English (Experiment 4) revealed that when identifying English stress pairs, Korean learners weighted vowel reduction more heavily than any suprasegmental cues. Both intensity and F0 were weighted in Korean learners’ perception; however, duration was not weighted at all, although younger Korean speakers still retain the phonemic vowel length distinction in their L1. Taken together, the current dissertation increases our understanding of the status of lexical stress in Korean, as well as the extent to which L2 learners produce and perceive L2 lexical stress by transferring prosodic features from their native language

Light-Controlled Cellular Internalization and Cytotoxicity of Nucleic Acid-Binding Agents: Studies in Vitro and in Zebrafish Embryos

This is the peer reviewed version of the following article: C. Penas, M. I. Sánchez, J. Guerra-Varela, L. Sanchez, M. E. Vázquez, J. L. Mascareñas, ChemBioChem 2016, 17, 37-41, which has been published in final form at https://doi.org/10.1002/cbic.201500455. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsWe synthesized octa‐arginine conjugates of DNA‐binding agents (bisbenzamidine, acridine and Thiazole Orange) and demonstrated that their DNA binding and cell internalization can be inhibited by appending a (negatively charged) oligoglutamic tail through a photolabile linker. UV irradiation released the parent conjugates, thus restoring cell internalization and biological activity. Assays with zebrafish embryos demonstrates the potential of this prodrug strategy for controlling in vivo cytotoxicityWe are thankful for the support given by the Spanish grants SAF2013–41943‐R, CTQ2012–31341 and CTQ2013–49317‐EXP, the Xunta de Galicia GRC2013–041, the ERDF and the European Research Council (Advanced Grant 340055). C.P. and M.I.S. thank the Spanish MCINN for their PhD fellowshipsS

Prediction of Obstructive Sleep Apnea Based on Respiratory Sounds Recorded Between Sleep Onset and Sleep Offset

Objectives To develop a simple algorithm for prescreening of obstructive sleep apnea (OSA) on the basis of respiratorysounds recorded during polysomnography during all sleep stages between sleep onset and offset. Methods Patients who underwent attended, in-laboratory, full-night polysomnography were included. For all patients, audiorecordings were performed with an air-conduction microphone during polysomnography. Analyses included allsleep stages (i.e., N1, N2, N3, rapid eye movement, and waking). After noise reduction preprocessing, data were segmentedinto 5-s windows and sound features were extracted. Prediction models were established and validated with10-fold cross-validation by using simple logistic regression. Binary classifications were separately conducted for threedifferent threshold criteria at apnea hypopnea index (AHI) of 5, 15, or 30. Prediction model characteristics, includingaccuracy, sensitivity, specificity, positive predictive value (precision), negative predictive value, and area under thecurve (AUC) of the receiver operating characteristic were computed. Results A total of 116 subjects were included; their mean age, body mass index, and AHI were 50.4 years, 25.5 kg/m2, and23.0/hr, respectively. A total of 508 sound features were extracted from respiratory sounds recorded throughoutsleep. Accuracies of binary classifiers at AHIs of 5, 15, and 30 were 82.7%, 84.4%, and 85.3%, respectively. Predictionperformances for the classifiers at AHIs of 5, 15, and 30 were AUC, 0.83, 0.901, and 0.91; sensitivity, 87.5%,81.6%, and 60%; and specificity, 67.8%, 87.5%, and 94.1%. Respective precision values of the classifiers were89.5%, 87.5%, and 78.2% for AHIs of 5, 15, and 30. Conclusion This study showed that our binary classifier predicted patients with AHI of ≥15 with sensitivity and specificityof >80% by using respiratory sounds during sleep. Since our prediction model included all sleep stage data, algorithmsbased on respiratory sounds may have a high value for prescreening OSA with mobile devices

miRTarBase: a database curates experimentally validated microRNA–target interactions

MicroRNAs (miRNAs), i.e. small non-coding RNA molecules (∼22 nt), can bind to one or more target sites on a gene transcript to negatively regulate protein expression, subsequently controlling many cellular mechanisms. A current and curated collection of miRNA–target interactions (MTIs) with experimental support is essential to thoroughly elucidating miRNA functions under different conditions and in different species. As a database, miRTarBase has accumulated more than 3500 MTIs by manually surveying pertinent literature after data mining of the text systematically to filter research articles related to functional studies of miRNAs. Generally, the collected MTIs are validated experimentally by reporter assays, western blot, or microarray experiments with overexpression or knockdown of miRNAs. miRTarBase curates 3576 experimentally verified MTIs between 657 miRNAs and 2297 target genes among 17 species. miRTarBase contains the largest amount of validated MTIs by comparing with other similar, previously developed databases. The MTIs collected in the miRTarBase can also provide a large amount of positive samples to develop computational methods capable of identifying miRNA–target interactions. miRTarBase is now available on http://miRTarBase.mbc.nctu.edu.tw/, and is updated frequently by continuously surveying research articles

Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.OAIID:RECH_ACHV_DSTSH_NO:T201615370RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A003535CITE_RATE:11.329FILENAME:4. ncomms12766.pdfDEPT_NM:농생명공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/fce63c4a-7de7-4741-996f-d8d24af38905/linkCONFIRM:

A Sound Approach to Language Matters: In Honor of Ocke-Schwen Bohn

The contributions in this Festschrift were written by Ocke’s current and former PhD-students, colleagues and research collaborators. The Festschrift is divided into six sections, moving from the smallest building blocks of language, through gradually expanding objects of linguistic inquiry to the highest levels of description - all of which have formed a part of Ocke’s career, in connection with his teaching and/or his academic productions: “Segments”, “Perception of Accent”, “Between Sounds and Graphemes”, “Prosody”, “Morphology and Syntax” and “Second Language Acquisition”. Each one of these illustrates a sound approach to language matters

Cell penetration, herbicidal activity, and in-vivo-toxicity of oligo-arginine derivatives and of novel guanidinium-rich compounds derived from the biopolymer cyanophycin Grogg, Marcel and Hilvert, Donald and Ebert, Marc-Olivier and Beck, Albert K. and Seebach, Dieter and Kurth, Felix and Dittrich, Petra S. and Sparr, C. and Wittlin, Sergio and Rottmann, Matthias and Mäser, Pascal

Oligo‐arginines are thoroughly studied cell‐penetrating peptides (CPPs, Figures 1 and 2). Previous in‐vitro investigations with the octaarginine salt of the phosphonate fosmidomycin (herbicide and anti‐malaria drug) have shown a 40‐fold parasitaemia inhibition with P. falciparum, compared to fosmidomycin alone (Figure 3). We have now tested this salt, as well as the corresponding phosphinate salt of the herbicide glufosinate, for herbicidal activity with whole plants by spray application, hoping for increased activities, i.e. decreased doses. However, both salts showed low herbicidal activity, indicating poor foliar uptake (Table 1). Another pronounced difference between in‐vitro and in‐vivo activity was demonstrated with various cell‐penetrating octaarginine salts of fosmidomycin: intravenous injection to mice caused exitus of the animals within minutes, even at doses as low as 1.4 μmol/kg (Table 2). The results show that use of CPPs for drug delivery, for instance to cancer cells and tissues, must be considered with due care. The biopolymer cyanophycin is a poly‐aspartic acid containing argininylated side chains (Figure 4); its building block is the dipeptide H‐βAsp‐αArg‐OH (H‐Adp‐OH). To test and compare the biological properties with those of octaarginines we synthesized Adp8‐derivatives (Figure 5). Intravenouse injection of H‐Adp8‐NH2 into the tail vein of mice with doses as high as 45 μmol/kg causes no symptoms whatsoever (Table 3), but H‐Adp8‐NH2 is not cell penetrating (HEK293 and MCF‐7 cells, Figure 6). On the other hand, the fluorescently labeled octamers FAM‐(Adp(OMe))8‐NH2 and FAM‐(Adp(NMe2))8‐NH2 with ester and amide groups in the side chains exhibit mediocre to high cell‐wall permeability (Figure 6), and are toxic (Table 3). Possible reasons for this behavior are discussed (Figure 7) and corresponding NMR spectra are presented (Figure 8)

Public preferences for corporate social responsibility activities in the pharmaceutical industry: Empirical evidence from Korea.

Although corporate social responsibility (CSR) activities are common in the pharmaceutical industry, there is little empirical evidence on consumer responses to CSR practices. We investigated public awareness, preferences, and expectations regarding social contribution of the pharmaceutical industry's CSR activities, and identified the factors associated with such activities. We conducted an online survey with 1,298 respondents comprising two groups: healthy individuals (546) and patients (752). Most respondents (78%) expressed interest in CSR activities undertaken by pharmaceutical companies. However, they reported a lack of awareness and experience thereof; only 26.9% were aware of and 7.9% had experience with such activities. Among our six CSR activity categories, both survey groups showed the highest preference for the "promoting public health" (healthy group: 6.34/10; patient group: 6.37/10) and "emergency disaster relief support" (6.31 and 6.35) categories. Among sub-categories, activities related to "development of innovative drugs in untreated areas" (6.63 and 6.82) and "support for research on new drug development" (6.59 and 6.84) received the highest scores. The mean expectation score of social contribution of all CSR activities was slightly higher than the mean preference score (6.37 and 6.06, respectively). The patient group exhibited a larger difference between the highest and lowest expectation scores than the healthy group (1.11 and 0.64, respectively). The results of the regression analysis revealed that being a patient, being male, and having positive attitudes toward CSR and its expected effects significantly and positively affected public preferences regarding CSR activities. We can conclude that CSR activities with high public preference might be an effective strategy to improve public awareness of the pharmaceutical industry's CSR activities. Furthermore, the highest preference for CSR activities relates to new drug development, indicating that our society believes the pharmaceutical industry's key CSR activity should be to pursue its intrinsic mission: to fulfill unmet medical needs by developing new drugs

Functional Outcomes of Cochlear Implantation in Children with Bilateral Cochlear Nerve Aplasia

Background and Objectives: Many otologists face a dilemma in the decision-making process of surgical management of patients with cochlear nerve (CN) aplasia. The goal of this study is to provide fresh evidence on cochlear implantation (CI) results in patients with CN aplasia. Materials and Methods: We scrutinized functional outcomes in 37 ears of 21 children with bilateral CN aplasia who underwent unilateral or bilateral CI based on cross-sectional and longitudinal assessments. Results: The Categories of Auditory Performance (CAP) scores gradually improved throughout the 3-year follow-up; however, variable outcomes existed between individuals. Specifically, 90% of recipients with a 1-year postoperative CAP score <= 1 could not achieve a CAP score over 1 even at 3-year postoperative evaluation, while the recipients with a 1-year postoperative CAP score >1 had improved auditory performance, and 72.7% of them were able to achieve a CAP score of 4 or higher. Meanwhile, intraoperative electrically evoked compound action potential was not correlated with postoperative CAP score. Conclusions: Our results further refine previous studies on the clinical feasibility of CI as the first treatment modality to elicit favorable auditory performance in children with CN aplasia. However, special attention should be paid to pediatric patients with an early postoperative CAP score <= 1 for identification of unsuccessful cochlear implants and switching to auditory brainstem implants.Y

Photoluminescent silicon nanoparticles ???as a self-reporting nanomedicine

Porous silicon nanoparticles (PSiNPs) have attracted increasing interest for imaging and treatment of diseases due to biocompatibility, large specific capacity for drug loading, non-toxic degradation products, and intrinsic photoluminescence (PL). In particular, the PL lifetime is typically on the order of microseconds, significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally presented in cells and tissues, thus allows discrimination of the silicon nanoparticle from the tissue autofluorescence. Herein, the long-lived PL is employed to monitor the status of drug payload elution, associated with biodegradation of the silicon nanocarriers, and demonstrated as a ???self-reporting??? system. Dissolution of the silicon matrix in physiological environment triggers drug release, along with decreasing intensity and blue shift of the PL spectra. Furthermore, by tracking the PL lifetime, the drug releasing status and the residual lifespan of the silicon nanocarriers are correspondingly acquired. The PL lifetime is a physically intensive property that can report only the inherent characteristics of the PSiNPs regardless of surrounding noise while the intensity-based reporting is substantially affected by many unwanted factors. We investigate a unique means to inform the lifespan of the PSiNPs as a biodegradable drug nanocarrier in vivo. This study presents a promising potential of the photoluminescent PSiNPs toward advanced drug delivery systems for translational medical platform including theranostics and visualized drug delivery tracking