The Impact of R10-Hydroxywarfarin on CYP2C9-Mediated S-Warfarin Metabolism

Thesis (Master's)--University of Washington, 2014

Poetry and feminine crafts in the letters of the young Marquise of Alorna (1750-1839)

abstract : Taking as a starting point the association between embroidery and language conveyed by the Greek myth of Filomela and Procne, this article examines the relationship between social status and ornaments like embroidery and lace. In order to illustrate this relationship an example is selected form the letters exchanged between the Marquise of Alorna and her Father where a connection is established between the production of these 'feminine' crafts, women's culture and womens writing, in the XVIIIth Century

Law’s spatial turn: geography, justice and a certain fear of space

This is a critical reading of the current literature on law and geography. The article argues that the literature is characterized by an undertheorization of the concept of space. The focus is either on the specific geography of law in the form of jurisdiction, or as a simple terminological innovation. Instead, the article suggests that law’s spatial turn ought to consider space as a singular parameter to the hitherto legal preoccupation with time, history and waiting. This forces law into dealing with a new, peculiarly spatial kind of uncertainty in terms of simultaneity, disorientation, materiality and exclusionary corporeal emplacement. The main area in which this undertheorization forcefully manifests itself is that of spatial justice. Despite its critical potential, the concept has been reduced by the majority of the relevant literature into another version of social, distributive or regional justice. On the contrary, if the peculiar characteristics of space are to be taken into account, a concept of justice will have to be rethought on a much more fundamental level than that.

Feminist epistemology meets the masculinity of marketing and consumer knowledge: a contemporary rendering of a decade-long debate

In this paper I outline possibilities for, and issues arising from, opposition towards the dominant ideologies and practices of marketing knowledge (Hirschman 1993) through an engagement with feminist epistemology (Longino 1991, Harding 1987). Feminist epistemology is a political branch of naturalised epistemology (Quine 1969) primarily concerned with critique of constructions of gender, gender norms and gendered interests within the production of knowledge (Anderson 1995) and with theorising, grounding and legitimating feminist knowledge making practices (Harding 1987). It is most often associated with the feminist critique of science, and with feminist science and technology studies (Haraway 1987, Wajman 1997). Feminist epistemology asks the question, ‘what is the nature of the feminist critical project as a way of knowing?’ (McLennan 1995:392). This paper outlines the basis of the feminist critique of knowledge generally, and as applied to marketing knowledge, offers description of the three main epistemological approaches to this question and suggestions for their application in practice. The paper progresses important work by consumer behaviour theorists (Bristor and Fischer 1993, Hirschman 1993) on the potentials of feminist ways of knowing for marketing and consumer behaviour by moving beyond the tripartite of feminist approaches outlined, and extending the discussion to take into account the development of situated knowledges theory (Haraway 1989, 1997), which has become so important in the decade since these papers were written. It joins ongoing conversations in consumer behaviour and marketing that share similar feminist concerns (Catterall et al 1997, 2000, 2005, Bettany and Woodruffe Burton 1999, 2005, and Hogg et al 1999, 2000) but in this contribution it takes a slightly tangential approach, seeing marketing knowledge in terms of its epistemic culture by using a model of masculinity in academic cultures from feminist theory (Wagner 1994) to help conceptualise it as such. The dominant masculine ideology of marketing knowledge both in execution (Penaloza 1994, Bristor and Fischer 1994, Fischer and Bristor 1993, Woodruffe 1996), and values (Hirschman 1993, Brown 2000, Desmond 1997) has been well documented over the past fifteen years. However, although the basis of this, how is it manifested and how a feminist informed marketing knowledge could be achieved, have been addressed somewhat in the literature (Bristor and Fischer 1993, Hogg, Bettany and Long 2000) an updated rendering is necessary which focuses specifically on epistemology and situates this discussion within a cultural framework. To do this I use the notions of cultural masculinity in academic disciplines developed by Wagner (1994) of ‘organisational egocentrism’, ‘fake collectivity’ and ‘de realisation’. With these, I raise important and specific issues around the notion of the masculinity of marketing knowledge, and then present an outline of feminist epistemologies to illustrate how different feminist approaches to knowledge would address these concerns.

A Bilingual Thesaurus of Everyday Life in Medieval England: Some Issues at the Interface of Semantics and Lexicography

This paper reports on issues at the interface between semantics and lexicography that arose out of the data collection and classification of vocabulary in Anglo-Norman and Middle English in order to create a bilingual thesaurus of everyday life in medieval England. The Bilingual Thesaurus project is based at Birmingham City University and the University of Westminster. Issues to be resolved included the definition of an occupational domain; the creation of a methodology of data collection; the delimitation of domain-specific vocabulary; making distinctions between sense and usage; and the categorisation of the lexical items. Some of these issues are general to thesaurus-making, some are specific to the making of historical thesauruses, while some are unique to the production of a thesaurus of two languages whose use overlapped for several centuries in the late medieval period in England.

Application of green zero-valent iron nanoparticles to the remediation of soils contaminated with ibuprofen

Zero-valent iron nanoparticles (nZVIs) are often used in environmental remediation. Their high surface area that is associated with their high reactivity makes them an excellent agent capable of transforming/degrading contaminants in soils and waters. Due to the recent development of green methods for the production of nZVIs, the use of this material became even more attractive. However, the knowledge of its capacity to degrade distinct types of contaminants is still scarce. The present work describes the study of the application of green nZVIs to the remediation of soils contaminated with a common anti-inflammatory drug, ibuprofen. The main objectives of this work were to produce nZVIs using extracts of grape marc, black tea and vine leaves, to verify the degradation of ibuprofen in aqueous solutions by the nZVIs, to study the remediation process of a sandy soil contaminated with ibuprofen using the nZVIs, and to compare the experiments with other common chemical oxidants. The produced nZVIs had nanometric sizes and were able to degrade ibuprofen (54 to 66% of the initial amount) in aqueous solutions. Similar remediation efficiencies were obtained in sandy soils. In this case the remediation could be enhanced (achieving degradation efficiencies above 95%) through the complementation of the process with a catalyzed nZVI Fenton-like reaction. These results indicate that this remediation technology represents a good alternative to traditional and more aggressive technologies.

Production of chitin-glucan complex by Pichia pastoris

Dissertation for the Degree of Master in Biotechnology

Production of polyhydroxyalkanoates from oil-containing substrates

Different oil-containing substrates, namely, used cooking oil (UCO), fatty acids-byproduct from biodiesel production (FAB) and olive oil deodorizer distillate (OODD) were tested as inexpensive carbon sources for the production of polyhydroxyalkanoates (PHA) using twelve bacterial strains, in batch experiments. The OODD and FAB were exploited for the first time as alternative substrates for PHA production. Among the tested bacterial strains, Cupriavidus necator and Pseudomonas resinovorans exhibited the most promising results, producing poly-3-hydroxybutyrate, P(3HB), form UCO and OODD and mcl-PHA mainly composed of 3-hydroxyoctanoate (3HO) and 3-hydroxydecanoate (3HD) monomers from OODD, respectively. Afterwards, these bacterial strains were cultivated in bioreactor. C. necator were cultivated in bioreactor using UCO as carbon source. Different feeding strategies were tested for the bioreactor cultivation of C. necator, namely, batch, exponential feeding and DO-stat mode. The highest overall PHA productivity (12.6±0.78 g L-1 day-1) was obtained using DO-stat mode. Apparently, the different feeding regimes had no impact on polymer thermal properties. However, differences in polymer‟s molecular mass distribution were observed. C. necator was also tested in batch and fed-batch modes using a different type of oil-containing substrate, extracted from spent coffee grounds (SCG) by super critical carbon dioxide (sc-CO2). Under fed-batch mode (DO-stat), the overall PHA productivity were 4.7 g L-1 day-1 with a storage yield of 0.77 g g-1. Results showed that SCG can be a bioresource for production of PHA with interesting properties. Furthermore, P. resinovorans was cultivated using OODD as substrate in bioreactor under fed-batch mode (pulse feeding regime). The polymer was highly amorphous, as shown by its low crystallinity of 6±0.2%, with low melting and glass transition temperatures of 36±1.2 and -16±0.8 ºC, respectively. Due to its sticky behavior at room temperature, adhesiveness and mechanical properties were also studied. Its shear bond strength for wood (67±9.4 kPa) and glass (65±7.3 kPa) suggests it may be used for the development of biobased glues. Bioreactor operation and monitoring with oil-containing substrates is very challenging, since this substrate is water immiscible. Thus, near-infrared spectroscopy (NIR) was implemented for online monitoring of the C. necator cultivation with UCO, using a transflectance probe. Partial least squares (PLS) regression was applied to relate NIR spectra with biomass, UCO and PHA concentrations in the broth. The NIR predictions were compared with values obtained by offline reference methods. Prediction errors to these parameters were 1.18 g L-1, 2.37 g L-1 and 1.58 g L-1 for biomass, UCO and PHA, respectively, which indicates the suitability of the NIR spectroscopy method for online monitoring and as a method to assist bioreactor control. UCO and OODD are low cost substrates with potential to be used in PHA batch and fed-batch production. The use of NIR in this bioprocess also opened an opportunity for optimization and control of PHA production process.

Fitness correlates with the extent of cheating in a bacterium.

There is growing awareness of the importance of cooperative behaviours in microbial communities. Empirical support for this insight comes from experiments using mutant strains, termed 'cheats', which exploit the cooperative behaviour of wild-type strains. However, little detailed work has gone into characterising the competitive dynamics of cooperative and cheating strains. We test three specific predictions about the fitness consequences of cheating to different extents by examining the production of the iron-scavenging siderophore molecule, pyoverdin, in the bacterium Pseudomonas aeruginosa. We create a collection of mutants that differ in the amount of pyoverdin that they produce (from 1% to 96% of the production of paired wild types) and demonstrate that these production levels correlate with both gene activity and the ability to bind iron. Across these mutants, we found that (1) when grown in a mixed culture with a cooperative wild-type strain, the relative fitness of a mutant is negatively correlated with the amount of pyoverdin that it produces; (2) the absolute and relative fitness of the wild-type strain in the mixed culture is positively correlated with the amount of pyoverdin that the mutant produces; and (3) when grown in a monoculture, the absolute fitness of the mutant is positively correlated with the amount of pyoverdin that it produces. Overall, we demonstrate that cooperative pyoverdin production is exploitable and illustrate how variation in a social behaviour determines fitness differently, depending on the social environment.

The effects of quinpirole in eliciting 50 kHz calls from the rat nucleus accumbens /

Fifty kHz rat vocalizations are theorized to reflect a positive affective state, and index the reward value of stimuli (Knutson, Burgdorf & Panksepp, 2002; Panksepp & Burgdorf, 2003; Brudzynski,2005). Previous studies have identified the neurochemical substrate of this behaviour to be dependent on dopaminergic activity at the nucleus accumbens shell (Burgdorf, Knutson, Panksepp & Ikemoto, 2001; Thompson, Leonard & Brudzynski, 2006). The utilization of d-amphetamine (a non-selective dopamine agonist) in these studies does not address the specific dopamine receptor types involved. The present study aims to identify the role of the D2- like family of receptors in the nucleus accumbens shell in the production of 50 kHz vocalizations in adult rats. Single injections of quinpirole in a saline vehicle were administered to the nucleus accumbens shell of 57 rats, and the number of 50 kHz vocalizations were recorded. An inverted V-shaped relationship was found between quinpirole dose (0.5 ~g, 3 ~g, 6 ~g, 1 0 ~g and 20 ~g, all in 0.2~1 saline) and the mean number of 50 kHz calls produced. Quinpirole successfully elicited significantly more 50 kHz calls than did a saline control at the 6 ~g dose, as did 7 ~g/0.2 ~l of d-amphetamine injections into the same brain site. To test whether a selective D2 antagonist could reverse elicited 50 kHz calling, double injections were given that used either saline or raclopride as a pretreatment before quinpirole injections. Saline followed by 6 ~g/0.2 ~l of quinpirole elicited significantly more 50 kHz vocalizations than did a double injection of saline, while pretreatment with an equimolar dose of raclopride reduced elicited calls to control levels. Raclopride was also used as a pretreatment of 7 ~g/0.2 ~l d-amphetamine, which elicited significantly fewer 50 kHz vocalizations than saline followed by amphetamine, replicating the finding of Thompson, Leonard & Brudzynski (2006).Subcutaneous injections of 0.5 mg/kg and 1.5 mg/kg of quinpirole produced a similar number of 50 kHz vocalizations as subcutaneous injection of saline. Wider dose ranges may be explored in fiiture research. Thus, direct activation of the Da-like receptors in the nucleus accumbens shell was sufficient to elicit 50 kHz vocalizations in adult rats, an effect which was reversed with selective local antagonism of Da-like receptors. The Da-like receptor family also appears necessary for pharmacological activation of 50 kHz calling, as d-amphetamine was no longer able to effectively elicit these vocalizations from the nucleus accumbens shell when the Da-receptor family was antagonized with raclopride. The acoustic parameters of elicited vocalizations remained typical of rat 50 kHz calls. Detailed analyses of the acoustic characteristics of elicited calls indicated significant increases in call duration and peak frequency across drug injection groups, particularly among quinpirole dose groups. The implications of these findings are not yet clear, but may represent an important direction for future research into the coding of semiotic content into affective signals in rats.

The effects of cultural conditions and parasitism on the lipid composition of choanephora cucubitarum (Berk. Rav.) thaxter /|nJohn M. Deven. -- 260 St. Catharines [Ont. : s. n.],

The fatty acid composition of the total, neutral, sterol, free fatty acid and polar-lipid fractions in the mycelium of Choanephora cucurbitarum was determined. The major fatty acids in all lipid fractions were palmitic, oleic, linoleic and y-linolenic acid. Different lipid fractions did not show any particular preference for any individual fatty acid; however, the degree of unsaturation was different in various lipid fractions. Addition of glutamic acid to the malt-yeast extract medium resulted in the biosynthesis of a number of long-chain fatty acids beyond y-linolenic acid. These fatty acids, e.g. C22~1' C24:0 and C26=Q were never observed to be present in the fungus when grown on a malt-yeast extract medium without glutamic acid. Furthermore, thin-layer chromatographic analysis showed a larger and denser spot of diphosphatidyl glycerol from the mycelium grown on the glutamic acid medium than from the control mycelium. Various cultural conditions such as temperature, age, pH, light and carbon:nitrogen ratio in the growth medium used in this study did not alter the qualitative profile of fatty acids normally present in the organism. Neither did these conditions stimulate the production of further long-chain fatty acids (C20 - C26) beyond y-linolenic acid as observed in growth media containing glutamic acid. These cultural conditions influenced the degree of unsaturation, this being due mainly to changes in the concentration of y-linolenic acid. The fatty acid pattern of the lipid fractions though the same qualitatively, differed quantitatively due to the variation in the y-linolenic acid content under different cultural conditions. The degree of unsaturation of various lipid fractions decreased with increases in temperature, light intensity and pH, but within each treatment the same pattern of decreasing degree of unsaturation with increasing age was observed. The cultural conditions, used in this study, are also known to influence the degree and rate of development of the parasite, Piptocephalis virginiana. A direct correlation was observed between the levels of y-linolenic acid in C. cucurbitarum during the early stages of growth (24 h) and the degree of parasitism of P. virginiana. The amount of y-linolenic acid present in the host mycelium was found to be unrelated to either the dry weight of the mycelium or to the total lipid contents. K. virginiana is confined to host species which produce y-linolenic acid in their mycelium. The lipid profile of the host, C. cucurbitarum, did not show a significant qualitative or quantitative change in the lipid profile as a result of infection by the parasite, P. virginiana,e However, an increase in the total lipid was observed in the infected host mycelium. The significance of these results is discussed.

Thermoaclimatory variations in the microenvironment of hemoglobin in the rainbow trout, Salmo gairdneri and the carp, Cyprinus carpio

Several inorganic substances (e.g., C£ , Mg , Ca , H ) are potent negative modulators of hemoglobin-oxygen affinity. To evaluate the possibility that potentially adaptive changes in the red cell ionic environment of hemoglobin may take place during acclimation of fishes to increased environmental temperature, hematological status (hemoglobin, hematocrit, red cell numbers, mean erythrocytic volume and hemoglobin content), plasma + + 2+ 2+ and packed red cell electrolyte levels (Na , K , Ca , Mg , C£ ) were evaluated in summer and winter populations of the stenothermal rainbow trout, Salmo gairdneri, following acclimation to 2°, 10°, 18°C, and in a spring population of eurythermal carp, Cyprinus carpio, held at 2°, 16° and 30°C. From these data cell ion concentrations and ion:hemoglobin ratios were estimated. In view of the role of red cell carbonic anhydrase in the reductions of blood C02 tensions and the recruitment of Na and C£~ lost by fishes, a preliminary investigation of thermoacclimatory changes in the activity of this system in rainbow trout erythrocytes was conducted. Few changes in hematological status were encountered following acclimation. There was, however, some evidence of weight-specific differential hematological response in carp. This lead to markedly greater increases in hemoglobin, hematocrit and red cell numbers in smaller rather than in larger specimens at higher temperatures; variations which were 2+ well correlated with changes in plasma Ca . Plasma composition in summer trout was not altered by acclimation. In winter trout plasma Na and K increased at higher temperatures. Carp were characterized by increases in plasma calcium, and reductions in sodium and magnesium under these conditions. Several significant seasonal differences in plasma ion levels were observed in the trout. (n) In trout, only erythrocytic K and K :Hb were altered by acclimation, rising at higher temperatures. In carp Na , Na :Hb, C£~ and C£~:Hb in- 2+ 2+ creased with temperature, while Mg and Mg :Hb declined. Changes in overall ionic composition in carp red cells were consistent with increases in H content. In both species significant reciprocal variations in C£~ 2+ - + and Mg were found. In mammalian systems increases in C£ and H reduce hemoglobin-oxygen affinity by interaction with hemoglobin. Reduction in 2+ 2+ Mg maximizes organophosphate modulator availability by decreasing ATP»Mg complex formation. Thus, the changes observed may be of adaptive value in reducing hemoglobin-oxygen affinity, and facilitating oxygen release to cells at higher temperatures. Trout appear to maintain a high chloridelow magnesium state over the entire thermal tolerance zone. Carp, however, achieved this state only at higher temperatures. In both species mean erythrocytic volume was decreased at higher temperatures and this may facilitate branchial oxygen loading. Since mean erythrocytic volume was inversely related to red cell ion content, it is hypothesized that reductions in cell volume are achieved by export of some unidentified solute or solutes. Variations in the carbonic anhydrase activity that could be attributed to the thermoacclimatory process were quite modest. On the other hand, assays performed at the temperature of acclimation showed a large temperature effect where under in vivo conditions of temperature fish acclimated to higher temperatures might be expected to have higher activities. Furthermore, since hematocrit increased with temperature in these fish, while carbonic anhydrase is present only in the erythrocyte, the whole blood levels of this enzyme are expected to increase and further augment the temperature effect. This, in turn, could aid in the reduction of C02 (111) tension and increase the production of H and HC0~~ used in the active uptake of Na and C£ at higher temperatures.

Kinetic and product studies for the oxidtion of organic sulfides and sulfoxides in the presence of transition metal complexes

Rates and products of the oxidation of diphenyl sulfide, phenyl methyl sulfide, p-chlorophenyl methyl sulfide and diphenyl sulfoxide have been determined. Oxidants included t-Bu02H alone, t-Bu02H plus molybdenum or vanadium catalysts and the molybdenum peroxo complex Mo0(02)2*HMPT. Reactions were chiefly carried out in ethanol at temperatures ranging from 20° to 65°C. Oxidation of diphenyl sulfide by t-Bu02H in absolute ethanol at 65°C followed second-order kinetics with k2 = 5.61 x 10 G M~1s"1, and yielded only diphenyl sulfoxide. The Mo(C0)g-catalyzed reaction gave both the sulfoxide and the sulfone with consecutive third-order kinetics. Rate = k3[Mo][t-Bu02H][Ph2S] + k^[Mo][t-Bu02H][Ph2S0], where log k3 = 12.62 - 18500/RT, and log k^ = 10.73 - 17400/RT. In the absence of diphenyl sulfide, diphenyl sulfoxide did not react with t-Bu02H plus molybdenum catalysts, but was oxidized by t-Bu02H-V0(acac)2. The uncatalyzed oxidation of phenyl methyl sulfide by t-Bu02H in absolute ethanol at 65°C gave a second-order rate constant, k = 3.48 x 10~"5 M^s""1. With added Mo(C0)g, the product was mainly phenyl methyl sulfoxide; Rate = k3[Mo][t-Bu02H][PhSCH3] where log k3 = 22.0 - 44500/RT. Both diphenyl sulfide and diphenyl sulfoxide react readily with the molybdenum peroxy complex, Mo0(02)2'HMPT in absolute ethanol at 35°C, yielding diphenyl sulfone. The observed features are mainly in agreement with the literature on metal ion-catalyzed oxidations of organic compounds by hydroperoxides. These indicate the formation of an active catalyst and the complexation of t-Bu02H with the catalyst. However, the relatively large difference between the activation energies for diphenyl sulfide and phenyl methyl sulfide, and the non-reactivity of diphenyl sulfoxide suggest the involvement of sulfide in the production of an active species.

Produced subjectivities and productive subjects : locating the potential of the self-reflective blog

Blogging software has popularly been used as a mode of writing about everyday life to interact with others. This thesis examines the political potentials that are opened up by self-reflective blogging. The self-reflective blog is a synergy of self-reflective practices and computer-mediated communication. A genealogy of the history of computer-mediated communication and various public self-reflective practices is conducted to uncover affect as the utility of various economies of subject production. Efforts made to blog-like the efforts made to interact online in other CMCs-are positioned as a kind of affective labor. Adapting Hardt and Negri's (2005) theorization of the multitude, whereby affective labor-the production of social relationshipsis a kind ofbiopolitical production, affect will be determined as a kind ofbiopolitical power that exists in everyday life.

The Role of Orexin-A in Anxiety and the Emission of Ultrasonic Vocalizations in Rats

Central administration of orexin-A has been shown to activate autonomic arousal in rats, reliably inducing anxiety-like behaviours in the open field. To date, there has yet to be a study investigating the role of orexin-A in the communication of such negative affective state. In the current study, forty-six adult male rats were chronically cannulated and administered orexin-A into the medial preoptic area/anterior hypothalamic area to determine the effect of this neuropeptide on anxiety-like behaviour and the production of 22 kHz aversive ultrasonic vocalizations. It was found that intracerebral administration of orexin-A increased autonomic arousal as measured by a significant increase in fecal boli output, however orexin-A did not significantly affect locomotor activity or induce 22 kHz calling. These data suggest that orexin-A is involved in the regulation of the autonomic aspect of anxiety-like behaviour but not in the vocal communication of such negative affect