Vowel Change across Noam Chomsky\u27s Lifespan

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

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

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

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

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:

Semienzymatic cyclization of disulfide-rich peptides using sortase A

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

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

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

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Preface

The University of Pennsylvania Working Papers in Linguistics (PWPL) is an occasional series published by the Penn Linguistics Club. The series has included volumes of previously unpublished work, or work in progress, by linguists with an ongoing affiliation with the Department, as well as volumes of papers from NWAV and the Penn Linguistics Colloquium. This volume contains selected papers from the 37th Penn Linguistics Colloquium, held from March 22nd-24th, 2013 in Philadelphia, PA at the University of Pennsylvania. Thanks go to the editorial board, in alphabetical order: Hezekiah Akiva Bacovcin, Haitao Cai, Mao-Hsu Chen, Eric Doty, Aaron Ecay, Sabriya Fisher, Amy Goodwin Davies, Guðrún Björg Gylfadóttir, Anton Karl Ingason, Helen Jeoung, Yong-Cheol Lee, Kobey Shwayder, Einar Freyr Sigurðsson, Elizabeth Sneller, Karen Tseng, Robert Wilder and David Wilson. Since Vol. 14.2, PWPL has been an internet-only publication. Since Vol. 13.2, PWPL has been published both in print and online gratis via ScholarlyCommons@Penn. Due to the large number of hits these online papers have received, and the time and expense of managing a back catalog of PWPL volumes, the editorial committee decided in 2008 to cease print publication in favor of wider-scale free online dissemination. Please continue citing PWPL papers or issues as you would a print journal article, though you may also provide the URL of the manuscript. An example is below: Ahern, Chris. 2014. Mergers, Migration, and Signaling. U. Penn Working Papers in Linguistics 20.1: Proceedings of PLC 37, ed. S. Kwon, 1-10. http://repository.upenn.edu/pwpl/vol20/iss1/2 The entire back catalog has been digitized and will be available on ScholarlyCommons@Penn soon. Publication in the University of Pennsylvania Working Papers in Linguistics (PWPL) does not preclude submission of papers elsewhere; copyright is retained by the author(s) of individual papers. The PWPL editors can be contacted at: U. Penn Working Papers in Linguistics 619 Williams Hall University of Pennsylvania Philadelphia, PA 19104–6305 [email protected] http://ling.upenn.edu/papers/pwpl.html Soohyun Kwon Issue Edito

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

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