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The purpose of this thesis is to explore the interaction between antibiotics at sub-lethal doses, and E.coli. Initially we focussed on pairwise antibiotic interaction, and the potential to exploit these interactions to minimise antibiotic resistance. In testing the hypothesis that antagonism will slow adaptation by reducing selection for resistance we determined that there are conditions in which this fails to be the case. We furthermore caution against treating drug interactions as anything other than a dynamic property of the bacteria-drug interaction, by showing that the relationship between two drugs may be both synergistic and antagonistic depending on a variety of factors. Whilst exploring the adaptive response to drug combinations we discovered a highly unusual effect of Doxycycline to act as a growth stimulant to E.coli AG100. Chapter 3 and 4 are devoted to determining the nature and mechanism of this stimulation, and analysing any potential genomic changes using whole genome re-sequencing. Having shown that dose response is not always a monotone function of increasing drug dose, in chapter 5 we also look at the dose response in a diffusive context, using a custom built imaging system to show the common non-monotonicity of disk diffusion type assays, that manifest themselves as bullseye patterns of growth. We use a mathematical model to explore the ecological and adaptive reasons for such patterns. Finally in chapter 6 we look at the coevolutionary history of phage and E.coli REL606 strains, by determining trade-offs caused by lambda phage and the sole carbon source maltotriose both utilising the same porin (lamB) for cell entry.

Field, greenhouse and laboratory experiments were implemented to investigate the effects of auxin herbicides on growth and yield of cotton in glyphosate based systems. Field experiments evaluated the effect of rate and timing of dicamba or 2,4-D exposure when applied in glyphosate-resistant cotton. Increasing rates of either dicamba or 2,4-D resulted in increased injury and yield reductions. Initial injury symptomology was similar for cotton exposed at vegetative and reproductive stages. When cotton was exposed to auxin herbicides during vegetative growth, injury increased with time, while foliar injury during reproductive growth was stagnant and often decreased with time. Subsequently, the strongest correlations to yield loss and injury were from later evaluations of vegetative timings. Recovery from injury due to auxin herbicide exposure was dependent upon favorable environmental conditions; however, recovery was often superficial and masked significant yield loss. Greenhouse studies evaluated the impact of the diglycolamine dicamba salt on the movement of 14C radio-labeled potassium salt glyphosate in barnyardgrass and johnsongrass. Increasing glyphosate rate increased total absorption of glyphosate in both species. Total absorption of glyphosate was not impacted by the presence of dicamba, for either johnsongrass or barnyardgrass. Dicamba did not consistently alter the translocation of glyphosate in johnsongrass; however, dicamba did reduce glyphosate translocation in barnyardgrass. Total amount of translocated glyphosate was 2.6 to 4.6% and 3.8 to 6.8% of applied in barnyardgrass and johnsongrass, respectively. Reduced translocation in barnyardgrass was a result of increased glyphosate accumulation in the distal portion of the treated leaf. Increasing the rate of glyphosate did overcome the dicamba induced antagonism; however, altered translocation of glyphosate has been documented to be a precursor to herbicide resistance.

Sociopolitical issues of mathematics education have not been a priority in research conducted in post-secondary contexts (Adiredja & Andrews-Larson, 2017; le Roux, 2009). When sociopolitical lenses are utilised, the focus is usually on issues of equity and mathematics is not viewed critically. At the same time, although mathematics education research has highlighted and scrutinised political aspects of mathematics education (e.g., Pais, 2012; Valero, 2004), mathematics is not always thought of as political, while there is little research focusing on how it has political features. This study adopts a critical approach to mathematics, in order to examine how mathematics is political in post-secondary contexts. Deriving its theoretical lens from Laclau and Mouffe (1985/2001, 1987; Mouffe, 2005), it views mathematics as a space in which meanings are negotiated and antagonisms take place, while at the same time other ways of meaning making are excluded. More specifically, I identify three features of mathematics which make it inextricably political: the values of mathematical knowledge (Bishop, 1991; Ernest, 2018, 2020; Skovsmose, 2020), the rationality of mathematics (Kollosche, 2014; Walkerdine, 1988), and the formatting function of mathematics (Barwell, 2013; Skovsmose, 1994b, 2000). I have conducted an empirical investigation of the ways in which mathematics is political within two post-secondary courses, an Introduction to Proofs and a Calculus course. Through a discourse analysis perspective based on the works of Foucault (1972), and Laclau and Mouffe (1985/2001, 1987), I explore how political features of mathematics are negotiated and established through the ways in which people interact in the context of the two courses. Findings indicate that mathematics is not a final product that students need to absorb, but it is instead a nexus of interconnected discourses which are not fixed or stable entities but rather are constantly shifting and contested social constructions. In the "Introduction to Proofs" course, I identified four overarching discourses: the "formalising as a prototype of rigour" discourse, the "diverse participation in mathematics" discourse, the "imaginary practice of mathematics" discourse, and the "efficacy of mathematical work/labour" discourse. In the Calculus course, the overarching discourses I identified were the "humanity of mathematics" discourse, the "applying mathematics" discourse, and the "the mathematics of the class and the mathematics of mathematicians" discourse. These discourses entail ontological, epistemological, and axiological aspects; are specific to a given time and place; and sometimes fit together nicely while in other cases can enter antagonistic relations. This work contributes to mathematics education literature by problematising the neutrality of mathematics and its consideration as apolitical in post-secondary contexts.

Fentanyl is a potent synthetic opioid that has been shown to produce sleep disturbances, and the deterioration of sleep quality is associated with drug abuse and relapse in humans. The hypocretin/orexin neuropeptide system is a plausible pharmacological target, and dual-hypocretin antagonists such as lemborexant may mitigate sleep disturbances associated with fentanyl dependence. The current study characterizes sleep macroarchitecture (time spent asleep or awake) and microarchitecture (the number of bouts, and NREM sleep spindle characterization) prior to fentanyl vapor exposure (baseline), following one week of drug abstinence, and four weeks of drug abstinence in female and male rats. Females and males showed a reduction in the amount of time spent in rapid eye movement (REM) sleep following one week of abstinence. The pre-treatment of lemborexant the following day increased the amount of time spent in REM, compared to vehicle at both one and four weeks of abstinence. While there was no effect of fentanyl abstinence on the amount of time spent in non-rapid eye movement (NREM) sleep and wakefulness, lemborexant increased the amount time spent in NREM and decreased the amount of time spent awake. Examination of microarchitecture demonstrated a decrease in the number of NREM bouts at one week of abstinence, which lemborexant subsequently brought back to baseline levels at weeks one and four. Abstinence from fentanyl did not impact the number of NREM sleep spindles, but indicated a trend showing a decrease in intra-spindle frequency at one week of abstinence. Lemborexant, however, increased the number of spindles at weeks one and four of abstinence. Presently, findings indicate that fentanyl abstinence produces changes in sleep macroarchitecture, particularly REM sleep disruptions, which may be alleviated by lemborexant. This highlights the need for further examination of the relationship between sleep disturbances and drug abstinence, and the use of dual-hypocretin antagonists as therapeutic intervention.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

The concentration of triclosan in antiseptics, disinfectants and preservatives in products exceeds the minimal lethal levels. Extensive use of triclosan and antibiotics results in bacterial resistance to their active ingredients. The precise relationship between use and resistance, however, has been challenging to define. The aim of the study was to identify and determine antibiotic resistance profiles of triclosan tolerant heterotrophic plate count bacteria isolates from sewage influent and effluent. R2 agar supplemented with triclosan was utilised to isolate the triclosan resistant bacteria. To determine the minimum inhibitory concentration (MIC), organisms were incubated for 24 hours at selected concentrations of triclosan. Polymerase chain reaction (PCR) amplification of the 16S rRNA region was done to identify isolates. An assay for cross resistance to various antibiotics was performed. Determination of enhanced resistance to antibiotics by adding antimicrobials to the medium will be performed by using three antibiotics. High performance liquid chromatography was conducted to quantified levels of triclosan persistent in sewage water. Forty-four isolates were resistant to levels of triclosan ranging from 0.25 mg/l to 0.5 mg/l. Minimum inhibitory concentration values of these isolates ranged from 0.125 mg/l to >1 mg/l of triclosan. 16S rDNA methods were used and five main genera namely, Bacillus, Pseudomonas, Enterococcus, Brevibacillus and Paenibacillus were identified. Cell wall targeting antibiotics showed more pronounced relation with the triclosan concentration. Relation to triclosan concentration is not as apparent with the antibiotic targeting protein synthesis. Combination of antimicrobials indicated that at certain triclosan concentrations synergism or antagonism is observed. The importance of applying the correct concentration and combination of antimicrobials is observed. Levels of triclosan were found throughout the sewage water. HPLC values indicated the presence of triclosan at post-grid removal and effluent of the WWTP. The triclosan concentrations decrease through the WWTP but small concentrations enter our water bodies. The presence of bacterial species that are resistant to high concentrations of triclosan and multiple antibiotics enter our natural water bodies and is cause for concern. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015

The concentration of triclosan in antiseptics, disinfectants and preservatives in products exceeds the minimal lethal levels. Extensive use of triclosan and antibiotics results in bacterial resistance to their active ingredients. The precise relationship between use and resistance, however, has been challenging to define. The aim of the study was to identify and determine antibiotic resistance profiles of triclosan tolerant heterotrophic plate count bacteria isolates from sewage influent and effluent. R2 agar supplemented with triclosan was utilised to isolate the triclosan resistant bacteria. To determine the minimum inhibitory concentration (MIC), organisms were incubated for 24 hours at selected concentrations of triclosan. Polymerase chain reaction (PCR) amplification of the 16S rRNA region was done to identify isolates. An assay for cross resistance to various antibiotics was performed. Determination of enhanced resistance to antibiotics by adding antimicrobials to the medium will be performed by using three antibiotics. High performance liquid chromatography was conducted to quantified levels of triclosan persistent in sewage water. Forty-four isolates were resistant to levels of triclosan ranging from 0.25 mg/l to 0.5 mg/l. Minimum inhibitory concentration values of these isolates ranged from 0.125 mg/l to >1 mg/l of triclosan. 16S rDNA methods were used and five main genera namely, Bacillus, Pseudomonas, Enterococcus, Brevibacillus and Paenibacillus were identified. Cell wall targeting antibiotics showed more pronounced relation with the triclosan concentration. Relation to triclosan concentration is not as apparent with the antibiotic targeting protein synthesis. Combination of antimicrobials indicated that at certain triclosan concentrations synergism or antagonism is observed. The importance of applying the correct concentration and combination of antimicrobials is observed. Levels of triclosan were found throughout the sewage water. HPLC values indicated the presence of triclosan at post-grid removal and effluent of the WWTP. The triclosan concentrations decrease through the WWTP but small concentrations enter our water bodies. The presence of bacterial species that are resistant to high concentrations of triclosan and multiple antibiotics enter our natural water bodies and is cause for concern. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015

Efter att ett debattinlägg undertecknat av Sverigedemokraternas partiledare publicerades i Aftonbladet i oktober 2009 började allt mer av mediernas utrymme att ägnas åt Sverigedemokraterna. Bland annat diskuterades vad som var lämpliga debattämnen när Sverigedemokraterna skulle bemötas.Syftet med denna undersökning är att undersöka vad dessa diskussioner kan ha för effekter på Sverigedemokraternas eventuella fram- eller motgång och vad detta innebär för det politiska klimatet. Fyra av de största dagstidningarna i Sverige har legat till grund för en diskursanalys. Analysen producerade sex teman debatten, samarbete, värderingar, verktyg, historia, och väljarna.Studien präglas av ett perspektiv som fokuserar på hegemonier och antagonistiska relationer. Vilket resulterade i upptäckten av ett antagonistiskt förhållande mellan Sverigedemokraterna och de etablerade politiska aktörerna. Sverigedemokraterna utestängs med moraliska medel och detta skapar en uppdelning mellan de moraliska och de omoraliska. Debatten om/med SD kan bidra till att det politiska fokuset vrids mot den sociokulturella konfliktdimensionen. Det råder viss konsensus bland skribenter och etablerade politiker att man bör samarbeta för att hindra Sverigedemokraterna från att kunna verka i Riksdagen.

Recent studies have demonstrated that an acute, low dose of ketamine, a non-competitive NMDA receptor antagonist, provides rapid and sustained antidepressant effects in patients with major depressive disorder. Studies in rodents have shown that the antidepressant properties of ketamine are due to an increase in dendritic spine density in the cortex. Our goal was to determine whether these effects are specific to ketamine and whether they are dependent on dose, drug regimen and brain region. We observed that the effects of ketamine on spine density were dependent on dose and drug regimen and were also brain region specific. In addition, MK-801, another NMDA receptor antagonist, did not demonstrate the same effects on spine density as ketamine. Furthermore, genetic NMDA receptor hypofunction significantly reduced spine density. Our studies demonstrate that while acute ketamine treatment leads to an increase in cortical spine density, chronic administration has opposite and potentially detrimental effects.