214 research outputs found

    Vowel Change across Noam Chomsky\u27s Lifespan

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    This study presents longitudinal acoustic evidence of how an adult speaker’s vowels change across his lifespan. Noam Chomsky was chosen as a speaker because he presents an excellent opportunity to study the effect of relocation to a different dialect area on adult phonology since he was born and raised in Philadelphia and moved to Boston in 1955. Two linguistic variables that have different phonemic systems in Philadelphia and Boston were examined in this study: i) /o/–/oh/ distinction in Philadelphia and /o/–/oh/ merger in Boston, ii) split short-a system (a phonemic distinction between tense and lax short-a with various phonological and lexical conditioning) in Philadelphia and nasal system (an allophonic alternation between a tense short-a before nasals and lax short-a before non-nasals) in Boston. Results based on Chomsky’s public speech in 1970 and 2009 show that his /o/ has significantly shifted along both F1 and F2 over 40 years, displaying a subphonemic shift, while /oh/ remained stable. For his short-a patterns, the 1970 pattern corresponds to neither a split nor a nasal system. In 2009, in contrast, a pattern similar to a nasal system emerged. It is suggested Chomsky was able to adopt features of a new ambient dialect over time as a result of contact with a second dialect well past the critical period

    The Development Of Glide Deletion In Seoul Korean: A Corpus And Articulatory Study

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    This dissertation investigates the pathways and causes of the development of glide deletion in Seoul Korean. Seoul provides fertile ground for studies of linguistic innovation in an urban setting since it has seen rapid historical, social and demographic changes in the twentieth century. The phenomenon under investigation is the variable deletion of the labiovelar glide /w/ found to be on the rise in Seoul Korean (Silva, 1991; Kang, 1997). I present two studies addressing variation and change at two different levels: a corpus study tracking the development of /w/-deletion at the phonological level and an articulatory study examining the phonetic aspect of this change. The corpus data are drawn from the sociolinguistic interviews with 48 native Seoul Koreans between 2015 and 2017. A trend comparison with the data from an earlier study of /w/- deletion (Kang, 1997) reveals that /w/-deletion in postconsonantal position has begun to retreat, while non-postconsonantal /w/-deletion has been rising vigorously. More importantly, the effect of preceding segment that used to be the strongest constraint on /w/-deletion has weakened over time. I conclude that /w/-deletion in Seoul Korean is being reanalyzed with the structural details being diluted over time. I analyze this weakening of the original pattern as the result of linguistic diffusion induced by a great influx of migrants into Seoul after the Korean War (1950-1953). In an articulatory study, ultrasound data of tongue movements and video data of lip rounding for the production of /w/ for three native Seoul Koreans in their 20s, 30s and 50s were analyzed using Optical Flow Analysis. I find that /w/ in Seoul Korean is subject to both gradient reduction and categorical deletion and that younger speakers exhibit a significantly larger articulatory gestures for /w/ after a bilabial than older generation, which is consistent with the pattern of phonological change found in the corpus study. This dissertation demonstrates the importance of using both corpus and articulatory data in the investigation of a change, finding the coexistence of gradient and categorical effects in segmental deletion processes. Finally, it advances our understanding of the outcome of migration-induced dialect contact in contemporary urban settings

    Semienzymatic cyclization of disulfide-rich peptides using sortase A

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    Background: Sortase A (SrtA) is a transpeptidase capable of catalyzing the formation of amide bonds. Results: SrtA was used to backbone-cyclize disulfide-rich peptides, including kalata B1, -conotoxin Vc1.1, and SFTI-1. Conclusion: SrtA-mediated cyclization is applicable to small disulfide-rich peptides. Significance: SrtA-mediated cyclization is an alternative to native chemical ligation for the cyclization of small peptides of therapeutic interest

    Changes in attitudes toward and patterns in traditional Korean medicine among the general population in South Korea: a comparison between 2008 and 2011

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    BACKGROUND: Traditional Korean medicine (TKM) is acknowledged to be prevalent among the Korean public, but few follow-up studies are available to confirm this commonly held belief. Whereas most survey studies have focused on the demographic factors influencing the usage of TKM, only a few studies have conducted a pattern or trend analysis over time. The purpose of this paper is to observe and document recent trends in the usage of TKM in South Korea and to compare overall patterns of TKM use over a period of several years. METHODS: A cross-sectional survey was conducted in 2011 to assess TKM usage patterns and public perceptions regarding TKM. An online questionnaire was administered to consenting respondents that focused upon individual preferences between TKM and current Western medicine, respondents’ reasons for using TKM, the frequency of respondents’ visits to TKM clinics, the reasons respondents visited TKM clinics, and respondents’ perceived satisfaction. RESULTS: The results revealed that 66.6% of the respondents showed a positive attitude toward TKM. In addition, 69.3% of the respondents had visited TKM clinics one to four times during the previous year. Patients used TKM with the intentions of receiving acupuncture (95.3%), moxibustion (40.1%), and cupping (36.0%) treatments or to take herbal medicines (35.7%). Most respondents who had visited TKM clinics were largely satisfied with the clinics’ effectiveness (56.1%). The factors most commonly associated with TKM usage included sex (female), age (50s), and education (college or higher), but the within-factor differences were not significant. Compared with a previous survey of other groups, TKM usage was found to have increased from 45.8% in 2008 to 69.3% in 2011. With the exception of acupuncture and physical therapy, most usage doubled or more than doubled. CONCLUSIONS: The attitudes toward and usage of TKM in South Korea have improved between 2008 and 2011. This result will be used to explain outcomes of certain social phenomena and to argue for national support in the promotion of TKM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1472-6882-14-436) contains supplementary material, which is available to authorized users

    Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

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    New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

    Coculture of Marine Streptomyces sp. With Bacillus sp. Produces a New Piperazic Acid-Bearing Cyclic Peptide

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    Microbial culture conditions in the laboratory, which conventionally involve the cultivation of one strain in one culture vessel, are vastly different from natural microbial environments. Even though perfectly mimicking natural microbial interactions is virtually impossible, the cocultivation of multiple microbial strains is a reasonable strategy to induce the production of secondary metabolites, which enables the discovery of new bioactive natural products. Our coculture of marine Streptomyces and Bacillus strains isolated together from an intertidal mudflat led to discover a new metabolite, dentigerumycin E (1). Dentigerumycin E was determined to be a new cyclic hexapeptide incorporating three piperazic acids, N-OH-Thr, N-OH-Gly, β-OH-Leu, and a pyran-bearing polyketide acyl chain mainly by analysis of its NMR and MS spectroscopic data. The putative PKS-NRPS biosynthetic gene cluster for dentigerumycin E was found in the Streptomyces strain, providing clear evidence that this cyclic peptide is produced by the Streptomyces strain. The absolute configuration of dentigerumycin E was established based on the advanced Marfey's method, ROESY NMR correlations, and analysis of the amino acid sequence of the ketoreductase domain in the biosynthetic gene cluster. In biological evaluation of dentigerumycin E (1) and its chemical derivatives [2-N,16-N-deoxydenteigerumycin E (2) and dentigerumycin methyl ester (3)], only dentigerumycin E exhibited antiproliferative and antimetastatic activities against human cancer cells, indicating that N-OH and carboxylic acid functional groups are essential for the biological activity

    Advancing the early detection of canine cognitive dysfunction syndrome with machine learning-enhanced blood-based biomarkers

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    Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans

    Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans

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    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:

    The Development of Glide Deletion in Seoul Korean: A Corpus and Articulatory Study

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    This dissertation investigates the pathways and causes of the development of glide deletion in Seoul Korean. Seoul provides fertile ground for studies of linguistic innovation in an urban setting since it has seen rapid historical, social and demographic changes in the twentieth century. The phenomenon under investigation is the variable deletion of the labiovelar glide /w/ found to be on the rise in Seoul Korean (Silva, 1991; Kang, 1997). I present two studies addressing variation and change at two different levels: a corpus study tracking the development of /w/-deletion at the phonological level and an articulatory study examining the phonetic aspect of this change. The corpus data are drawn from the sociolinguistic interviews with 48 native Seoul Koreans between 2015 and 2017. A trend comparison with the data from an earlier study of /w/- deletion (Kang, 1997) reveals that /w/-deletion in postconsonantal position has begun to retreat, while non-postconsonantal /w/-deletion has been rising vigorously. More importantly, the effect of preceding segment that used to be the strongest constraint on /w/-deletion has weakened over time. I conclude that /w/-deletion in Seoul Korean is being reanalyzed with the structural details being diluted over time. I analyze this weakening of the original pattern as the result of linguistic diffusion induced by a great influx of migrants into Seoul after the Korean War (1950-1953). In an articulatory study, ultrasound data of tongue movements and video data of lip rounding for the production of /w/ for three native Seoul Koreans in their 20s, 30s and 50s were analyzed using Optical Flow Analysis. I find that /w/ in Seoul Korean is subject to both gradient reduction and categorical deletion and that younger speakers exhibit a significantly larger articulatory gestures for /w/ after a bilabial than older generation, which is consistent with the pattern of phonological change found in the corpus study. This dissertation demonstrates the importance of using both corpus and articulatory data in the investigation of a change, finding the coexistence of gradient and categorical effects in segmental deletion processes. Finally, it advances our understanding of the outcome of migration-induced dialect contact in contemporary urban settings
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