258 research outputs found

    The experimental state of mind in elicitation: illustrations from tonal fieldwork

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    This paper illustrates how an “experimental state of mind”, i.e. principles of experimental design, can inform hypothesis generation and testing in structured fieldwork elicitation. The application of these principles is demonstrated with case studies in toneme discovery. Pike’s classic toneme discovery procedure is shown to be a special case of the application of experimental design. It is recast in two stages: (1) the inference of the hidden structure of tonemes based on unexplained variability in the pitch contour r emaining, even after other sources of influence on the pitch contour are accounted for, and (2) the confirmation of systematic effects of hypothesized tonal classes on the pitch contour in elicitations structured to control for confounding variables that could obscure the relati on between tonal classes and the pitch contour. Strategies for controlling the confounding variables, such as blocking and randomization, are discussed. The two stages are exemplified using data elicited from the early stages of toneme discovery in Kirikiri, a language of New Guinea. *This paper is in the series How to Study a Tone Language, edited by Steven Bird and Larry HymanNational Foreign Language Resource Cente

    Computational Perspectives on Phonological Constituency and Recursion

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    Whether or not phonology has recursion is often conflated with whether or not phonology has strings or trees as data structures. Taking a computational perspective from formal language theory and focusing on how phonological strings and trees are built, we disentangle these issues. We show that even considering the boundedness of words and utterances in physical realization and the lack of observable examples of potential recursive embedding of phonological constituents beyond a few layers, recursion is a natural consequence of expressing generalization in phonological grammars for strings and trees. While prosodically-conditioned phonological patterns can be represented using grammars for strings, e.g., with bracketed string representations, we show how grammars for trees provide a natural way to express these patterns and provide insight into the kinds of analyses that phonologists have proposed for them.Que la fonologia mostri o no recursivitat sovint va lligat al fet que tingui o no cadenes o arbres en l'estructura de les seves dades. A partir de la perspectiva computacional de la teoria formal del llenguatge i tenint en compte com es construeixen les cadenes i els arbres fonològics, mirem de destriar aquestes qüestions. Mostrem que, fins i tot tenint en compte la limitació de paraules i enunciats en la realització física i la manca d'exemples observables d'incorporació recursiva potencial de constituents fonològics més enllà d'unes poques capes, la recursivitat és una conseqüència natural de l'expressió de generalitzacions fonològiques per a cadenes i arbres. Tot i que els patrons fonològics condicionats prosòdicament es poden representar utilitzant gramàtiques per a cadenes, per exemple amb representacions amb claudàtors, mostrem com les gramàtiques amb arbres proporcionen una manera natural d'expressar aquests patrons i proporcionen coneixement rellevant sobre els tipus d'anàlisis d'aquests patrons que s'han proposat des de la fonologia

    Investigation of the Effect of Contextual Factors on BIN Production in AAE

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    Treatments of African American English (AAE) in the literature have focused primarily on morphosyntactic differences from mainstream American English. One these differences is found in the tense and aspect system. While both dialects have the present perfect use for “been”, AAE also has a stressed variant of “been”, termed BIN. This aspectual marker is featured in the literature, but the main focus has been on its prosodic qualities. It differs from present perfect been in that it has the semantics of a remote past marker (Rickford 1973, Rickford 1975, Green 1998). For a comprehensive understanding of AAE’s tense aspect system, both syntactic-semantic and discourse-pragmatic aspects of these markers need to be studied as well. We complete a production experiment with members of an AAE-speaking community in Southwest Louisiana followed by an acceptability judgement task. The purpose of the experiment is twofold. First, it allows us to examine BIN production in canonical BIN environments and non-BIN environments. Second, by paying close attention to the context these environments occur in, we can also examine the influence of discourse-pragmatic factors (LONG-TIME, TEMPORAL JUST, POLAR QUESTIONS) on BIN production in unambiguous environments, as well as in ambiguous environments. The factors LONG-TIME and TEMPORAL JUST are found to be significant predictors of BIN production Furthermore, there is a significant difference in ambiguity, such that the unambiguous contexts predicted BIN slightly less. Overall, the results of the experiment suggest that speakers are consistent in their BIN production for expected BIN environments, but more variable in the non-BIN environments for both unambiguous and ambiguous contexts. This raises the interesting question of why speakers are more variable in the non-BIN environments as well as questioning what the discourse-pragmatic factors are actually capturing. Together, however, it suggests that there are a variety of components that can influence BIN production. Future areas of work could further investigate in regards these components

    Individual and Collective Contributions of Chaperoning and Degradation to Protein Homeostasis in E. coli

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    SummaryThe folding fate of a protein in vivo is determined by the interplay between a protein’s folding energy landscape and the actions of the proteostasis network, including molecular chaperones and degradation enzymes. The mechanisms of individual components of the E. coli proteostasis network have been studied extensively, but much less is known about how they function as a system. We used an integrated experimental and computational approach to quantitatively analyze the folding outcomes (native folding versus aggregation versus degradation) of three test proteins biosynthesized in E. coli under a variety of conditions. Overexpression of the entire proteostasis network benefited all three test proteins, but the effect of upregulating individual chaperones or the major degradation enzyme, Lon, varied for proteins with different biophysical properties. In sum, the impact of the E. coli proteostasis network is a consequence of concerted action by the Hsp70 system (DnaK/DnaJ/GrpE), the Hsp60 system (GroEL/GroES), and Lon

    TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

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    Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR
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