CYP2D6 inherited variation and inhibiting medication use in relation to adverse breast cancer outcomes after tamoxifen therapy

Thesis (Master's)--University of Washington, 2016-06

From postgraduate student to published writer:discourse variation and development in TESOL

This thesis is part of a project whose overall aim is to assist participants on an MSc TESOL course who wish to begin to publish articles in the field to do so. The project, which is undertaken within a naturalistic paradigm, has two intimately related and mutually constitutive strands: one descriptive, one interventionist. The descriptive strand consists of an analytical model of the TESOL article genre, and it is instantiated in this thesis. The interventionist strand consists of a series of pedagogic interactions and materials intended to assist project participants formulate a text suitable for publication within the target genre, and it is reported on in this thesis. I begin the thesis by looking in detail at the research approach which characterises the project. I then attempt to explain the situational context of the work and to position it within the context of other research in the areas of discourse community membership, academic genres, genre learning and academic enculturation. Having thus contextualised the work, I next attempt a detailed exploration of the problems of postgraduate students in TESOL when first attempting to write in the TESOL article genre: this exploration is undertaken from both a linguistic and a pedagogic perspective. Then in subsequent chapters, both a linguistic and a pedagogic response to these problems are proposed: the first consisting of an analytical model of the target genre, the second consisting of a series of pedagogic interactions and materials. The relationships between the two lines of response are also examined in some detail. Then in the final part of the thesis, I report feedback from the interventionist strand and attempt to conduct an evaluation of the whole project to date. Criteria for evaluation are proposed and examined in some detail in the context of the research approach of the project. The concluding chapter is a brief discussion of future directions for this work.

Formant-frequency variation and its effects on across-formant grouping in speech perception

How speech is separated perceptually from other speech remains poorly understood. In a series of experiments, perceptual organisation was probed by presenting three-formant (F1+F2+F3) analogues of target sentences dichotically, together with a competitor for F2 (F2C), or for F2+F3, which listeners must reject to optimise recognition. To control for energetic masking, the competitor was always presented in the opposite ear to the corresponding target formant(s). Sine-wave speech was used initially, and different versions of F2C were derived from F2 using separate manipulations of its amplitude and frequency contours. F2Cs with time-varying frequency contours were highly effective competitors, whatever their amplitude characteristics, whereas constant-frequency F2Cs were ineffective. Subsequent studies used synthetic-formant speech to explore the effects of manipulating the rate and depth of formant-frequency change in the competitor. Competitor efficacy was not tuned to the rate of formant-frequency variation in the target sentences; rather, the reduction in intelligibility increased with competitor rate relative to the rate for the target sentences. Therefore, differences in speech rate may not be a useful cue for separating the speech of concurrent talkers. Effects of competitors whose depth of formant-frequency variation was scaled by a range of factors were explored using competitors derived either by inverting the frequency contour of F2 about its geometric mean (plausibly speech-like pattern) or by using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Competitor efficacy depended on the overall depth of frequency variation, not depth relative to that for the other formants. Furthermore, the triangle-wave competitors were as effective as their more speech-like counterparts. Overall, the results suggest that formant-frequency variation is critical for the across-frequency grouping of formants but that this grouping does not depend on speech-specific constraints.

Formant-frequency variation and its effects on across-formant grouping in speech perception

How speech is separated perceptually from other speech remains poorly understood. In a series of experiments, perceptual organisation was probed by presenting three-formant (F1+F2+F3) analogues of target sentences dichotically, together with a competitor for F2 (F2C), or for F2+F3, which listeners must reject to optimise recognition. To control for energetic masking, the competitor was always presented in the opposite ear to the corresponding target formant(s). Sine-wave speech was used initially, and different versions of F2C were derived from F2 using separate manipulations of its amplitude and frequency contours. F2Cs with time-varying frequency contours were highly effective competitors, whatever their amplitude characteristics, whereas constant-frequency F2Cs were ineffective. Subsequent studies used synthetic-formant speech to explore the effects of manipulating the rate and depth of formant-frequency change in the competitor. Competitor efficacy was not tuned to the rate of formant-frequency variation in the target sentences; rather, the reduction in intelligibility increased with competitor rate relative to the rate for the target sentences. Therefore, differences in speech rate may not be a useful cue for separating the speech of concurrent talkers. Effects of competitors whose depth of formant-frequency variation was scaled by a range of factors were explored using competitors derived either by inverting the frequency contour of F2 about its geometric mean (plausibly speech-like pattern) or by using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Competitor efficacy depended on the overall depth of frequency variation, not depth relative to that for the other formants. Furthermore, the triangle-wave competitors were as effective as their more speech-like counterparts. Overall, the results suggest that formant-frequency variation is critical for the across-frequency grouping of formants but that this grouping does not depend on speech-specific constraints. © Springer Science+Business Media New York 2013.

Dialect variation

Relatively little research on dialect variation has been based on corpora of naturally occurring language. Instead, dialect variation has been studied based primarily on language elicited through questionnaires and interviews. Eliciting dialect data has several advantages, including allowing for dialectologists to select individual informants, control the communicative situation in which language is collected, elicit rare forms directly, and make high-quality audio recordings. Although far less common, a corpus-based approach to data collection also has several advantages, including allowing for dialectologists to collect large amounts of data from a large number of informants, observe dialect variation across a range of communicative situations, and analyze quantitative linguistic variation in large samples of natural language. Although both approaches allow for dialect variation to be observed, they provide different perspectives on language variation and change. The corpus- based approach to dialectology has therefore produced a number of new findings, many of which challenge traditional assumptions about the nature of dialect variation. Most important, this research has shown that dialect variation involves a wider range of linguistic variables and exists across a wider range of language varieties than has previously been assumed. The goal of this chapter is to introduce this emerging approach to dialectology. The first part of this chapter reviews the growing body of research that analyzes dialect variation in corpora, including research on variation across nations, regions, genders, ages, and classes, in both speech and writing, and from both a synchronic and diachronic perspective, with a focus on dialect variation in the English language. Although collections of language data elicited through interviews and questionnaires are now commonly referred to as corpora in sociolinguistics and dialectology (e.g. see Bauer 2002; Tagliamonte 2006; Kretzschmar et al. 2006; D'Arcy 2011), this review focuses on corpora of naturally occurring texts and discourse. The second part of this chapter presents the results of an analysis of variation in not contraction across region, gender, and time in a corpus of American English letters to the editor in order to exemplify a corpus-based approach to dialectology.

The Spanish Spoken in Cuba: Antecedents, Processes of Phonetic Variation, and Cubanisms- Lecture by Elizabeth Santana Cepero

The flyer promotes " The Spanish Spoken in Cuba: Antecedents, Processes of Phonetic Variation, and Cubanisms", a lecture by Elizabeth Santana Cepero on the Cuban variety of Spanish that results from historical and socoiolinguistic processes of transculturation and change. The lecture was conducted in Spanish and held on November 19,2015 at FIU Modesto A. Maidique Campus Green Library 220.

WOOD DENSITY VARIATION AND TREE RING DEMARCATION IN Gmelina arborea TREES USING X-RAY DENSITOMETRY

Due to its relationship with other properties, wood density is the main wood quality parameter. Modern, accurate methods - such as X-ray densitometry - are applied to determine the spatial distribution of density in wood sections and to evaluate wood quality. The objectives of this study were to determinate the influence of growing conditions on wood density variation and tree ring demarcation of gmelina trees from fast growing plantations in Costa Rica. The wood density was determined by X-ray densitometry method. Wood samples were cut from gmelina trees and were exposed to low X-rays. The radiographic films were developed and scanned using a 256 gray scale with 1000 dpi resolution and the wood density was determined by CRAD and CERD software. The results showed tree-ring boundaries were distinctly delimited in trees growing in site with rainfall lower than 25 10 mm/year. It was demonstrated that tree age, climatic conditions and management of plantation affects wood density and its variability. The specific effect of variables on wood density was quantified by for multiple regression method. It was determined that tree year explained 25.8% of the total variation of density and 19.9% were caused by climatic condition where the tree growing. Wood density was less affected by the intensity of forest management with 5.9% of total variation.

Morphological variation and reproductive incompatibility of three coconut-mite-associated populations of predatory mites identified as Neoseiulus paspalivorus (Acari: Phytoseiidae)

Predatory mites identified as Neoseiulus paspalivorus DeLeon (Phytoseiidae) have been considered as agents for classical biological control of the coconut mite, Aceria guerreronis Keifer (Eriophyidae), in Africa and elsewhere. Preliminary identification of geographically distinct populations as belonging to the same species (N. paspalivorus) was based on their morphological similarity. However, laboratory studies recently conducted have shown large differences in feeding behaviors and biological characteristics among individuals collected from three geographic origins: Brazil (South America), Benin and Ghana (West Africa). As morphologically similar specimens do not necessarily belong to the same species, we evaluated under laboratory conditions, reproductive compatibility between the specimens from three geographic locations to ascertain their conspecificity. Morphological measurements were also made to determine whether there is a means of discriminating between them. Inter-population crosses showed complete reproductive isolation between the three geographic populations, but interpopulation discontinuities in morphometric characters were absent. These results indicate that the tested specimens are distinct biological entities despite morphological similarity. Further molecular genetic studies are therefore proposed, including screening for endosymbionts and assessment of genetic differentiation, to determine the cause of reproductive incompatibility and to clarify the taxonomic relationship between those populations.

Snake venomics and antivenomics of Crotalus durissus subspecies from Brazil: Assessment of geographic variation and its implication on snakebite management

We report the comparative proteomic and antivenomic characterization of the venoms of subspecies cascavella and collilineatus of the Brazilian tropical rattlesnake Crotalus durissus. The venom proteomes of C. d. collilineatus and C. d. cascavella comprise proteins in the range of 4-115 kDa belonging to 9 and 8 toxin families, respectively. Collilineatus and cascavella venoms contain 20-25 main toxins belonging to the following protein families: disintegrin, PLA(2), serine proteinase, cysteine-rich secretory protein (CRISP), vascular endothelial growth factor-like (VEGF), L-amino acid oxidase, C-type lectin-like, and snake venom metalloproteinase (SVMP). As judged by reverse-phase HPLC and mass spectrometry, cascavella and collilineatus share about 90% of their venom proteome. However, the relative occurrence of the toxin families departs among the two C. durissus subspecies venoms. The most notable difference is the presence of the myotoxin crotamine in some C. d. collilineatus specimens (averaging 20.8% of the total proteins of pooled venom), which is absent in the venom of C. d. cascavella. On the other hand, the neurotoxic PLA2 crotoxin represents the most abundant protein in both C. durissus venoms, comprising 67.4% of the toxin proteome in C. d. collilineatus and 72.5% in C. d. cascavella. Myotoxic PLA(2)s are also present in the two venoms albeit in different relative concentrations (18.1% in C. d. cascavella vs. 4.6% in C. d. collilineatus). The venom composition accounts for the clinical manifestations caused by C. durissus envenomations: systemic neurotoxicity and myalgic symptoms and coagulation disturbances, frequently accompanied by myoglobinuria and acute renal failure. The overall compositions of C. d. subspecies cascavella and collilineatus venoms closely resemble that of C. d. terrificus, supporting the view that these taxa can be considered geographical variations of the same species. Pooled venom from adult C.d. cascavella and neonate C.d. terrificus lack crotamine, whereas this skeletal muscle cell membrane depolarizing inducing myotoxin accounts for similar to 20% of the total toxins of venom pooled from C.d. collilineatus and C.d. terrificus from Southern Brazil. The possible relevance of the observed venom variability among the tropical rattlesnake subspecies was assessed by antivenomics using anti-crotalic antivenoms produced at Instituto Butantan and Instituto Vital Brazil. The results revealed that both antivenoms exhibit impaired immunoreactivity towards crotamine and display restricted (similar to 60%) recognition of PLA(2) molecules (crotoxin and D49-myotoxins) from C. d. cascavella and C. d. terrificus venoms. This poor reactivity of the antivenoms may be due to a combination of factors: on the one hand, an inappropriate choice of the mixture of venoms for immunization and, on the other hand, the documented low immunogenicity of PLA(2) molecules. C. durissus causes most of the lethal snakebite accidents in Brazil. The implication of the geographic variation of venom composition for the treatment of bites by different C. durissus subspecies populations is discussed. (C) 2010 Elsevier B.V. All rights reserved.

Norwegian long-distance reflexives: Lectal variation and speaker attitudes

10 lectal variables were examined with respect to Norwegian speakers' acceptance of long-distance reflexives (LDR), using a questionnaire to elicit grammaticality judgements on 50 potential LDR sentences. A sample of 180 speakers completed the questionnaire. The data was analysed using a general linear model univariate model, and Spearman's correlation. In this sample the results showed that dialect and level of education had significant effects on speakers' acceptance of long-distance reflexives, while sex, age, being a native speaker, having both native-speaker parents, living in the city or the country, and the speaker's attitudes to the two Norwegian writing languages had no influence on speakers' acceptance of long-distance reflexives. It is suggested that the influence of Danish on Norwegian writing and on the southern dialects may be the cause of the observed variation with respect to LDR in Norwegian.

Geographic variation and positive selection on M7 lysin, an acrosomal sperm protein in mussels (Mytilus spp.)

Successful fertilization in free-spawning marine organisms depends on the interactions between genes expressed on the surfaces of eggs and sperm. Positive selection frequently characterizes the molecular evolution of such genes, raising the possibility that some common deterministic process drives the evolution of gamete recognition genes and may even be important for understanding the evolution of prezygotic isolation and speciation in the marine realm. One hypothesis is that gamete recognition genes are subject to selection for prezygotic isolation, namely reinforcement. In a previous study, positive selection on the gene coding for the acrosomal sperm protein M7 lysin was demonstrated among allopatric populations of mussels in the Mytilus edulis species group (M. edulis, M. galloprovincialis, and M. trossulus). Here, we expand sampling to include M7 lysin haplotypes from populations where mussel species are sympatric and hybridize to determine whether there is a pattern of reproductive character displacement, which would be consistent with reinforcement driving selection on this gene. We do not detect a strong pattern of reproductive character displacement; there are no unique haplotypes in sympatry nor is there consistently greater population structure in comparisons involving sympatric populations. One distinct group of haplotypes, however, is strongly affected by natural selection and this group of haplotypes is found within M. galloprovincialis populations throughout the Northern Hemisphere concurrent with haplotypes common to M. galloprovincialis and M. edulis. We suggest that balancing selection, perhaps resulting from sexual conflicts between sperm and eggs, maintains old allelic diversity within M. galloprovincialis.

Geographic call variation and further notes on habitat of Ameerega flavopicta (Anura, Dendrobatidae)

We describe habitat and inter-populational call variation of the dendrobatid frog Ameerega flavopicta. Data were collected in the Brazilian states ofminas Gerais and Goias. Principal component analysis separated the Goias population from others because of its higher call rates and shorter calls. The Paranaiba Rivermay represent themajor geographic barrier. We recognize the cephalic amplexus as themain type for the species. Although habitat disturbances increased since 1990, we did not notice differences in the density of callingmales at Serra do Cipo. Ameerega flavopicta appears to be quite resistant to alterations in its natural habitats caused by human activities.

A Comparison Between Pulse Pressure Variation and Right End Diastolic Volume Index as Guides to Resuscitation in a Model of Hemorrhagic Shock in Pigs

Background: Different hemodynamic parameters including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally induced hemorrhagic shock. Methods: Twenty-six anesthetized and mechanically ventilated pigs were allocated into control (group I), PPV (group II), or RVEDVI (group III) group. Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40 mm Hg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, 60 minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), 1 hour and 2 hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on analysis of variance for repeated measures followed by the Bonferroni test (p < 0.05). Results: Volume and time to resuscitation were higher in group III than in group II (group III = 1,305 +/- 331 mL and group II = 965 +/- 245 mL, p < 0.05; and group III = 24.8 +/- 4.7 minutes and group II = 8.8 +/- 1.3 minutes, p < 0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. Conclusion: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.

Cell cycle model to describe animal cell size variation and lag between cell number and biomass dynamics

The use of cell numbers rather than mass to quantify the size of the biotic phase in animal cell cultures causes several problems. First, the cell size varies with growth conditions, thus yields expressed in terms of cell numbers cannot be used in the normal mass balance sense. Second, experience from microbial systems shows that cell number dynamics lag behind biomass dynamics. This work demonstrates that this lag phenomenon also occurs in animal cell culture. Both the lag phenomenon and the variation in cell size are explained using a simple model of the cell cycle. The basis for the model is that onset of DNA synthesis requires accumulation of G1 cyclins to a prescribed level. This requirement is translated into a requirement for a cell to reach a critical size before commencement of DNA synthesis. A slower gl-owing cell will spend more time in G1 before reaching the critical mass. In contrast, the period between onset of DNA synthesis and mitosis, tau(B), is fixed. The two parameters in the model, the critical size and tau(B), were determined from eight steady-state measurements of mean cell size in a continuous hybridoma culture. Using these parameters, it was possible to predict with reasonable accuracy the transient behavior in a separate shift-up culture, i.e., a culture where cells were transferred from a lean environment to a rich environment. The implications for analyzing experimental data for animal cell culture are discussed. (C) 1997 John Wiley & Sons, Inc.