“STRANGE SIMILES”: THE FAERIE OUEENE AND RENAISSANCE NATURAL HISTORY

Animals appear in every canto of every book of The Faerie Queene. This dissertation seeks to accentuate the strangeness of Spenser’s animals as well as to counter it. By placing Spenser’s epic in dialogue with early modem natural history, with which it shares a constant didacticism, I argue that the strangeness of his animals must first be recognized and then remedied by learning what was “meant” by those animals in the culture Spenser inhabited and helped make. Chapter One proposes ways in which Spenser, inhabiting a particular cultural time, place, and position, could have learned natural history as part of his formal education. Chapter Two argues for the centrality of exemplary symbolism in the presiding attitudes towards animals held during Spenser’s lifetime and how the practices and products of natural history embody these attitudes. Chapters Three and Four engage directly with two representative animals from Spenser’s poem, the lion and the crocodile, showing that animals are not merely imaginative conveniences but instead are complex, culturally encoded signifiers. The thesis also includes an appended compendium of all the animals of The Faerie Queene

Up Schitt’s Creek?: Comedy as a slantwise pedagogical encounter with queerness

Pedagogical approaches to learning about LGBTQI+ themes and experiences remain a largely under-studied topic in teacher education. In response to this gap, the purpose of this paper is to offer reflections on the pedagogical value of comedy for exploring such themes and experiences in teacher education, focusing especially on the situational comedy (sitcom) Schitt’s Creek. We suggest that the sitcom offers teacher education an opportunity for ‘slantwise’ pedagogical encounters with LGBTQI+ themes and experiences, i.e., non-affronting encounters that resist damage-centred narratives of LGBTQI+ people and are open to multiple queer futures. In exploring how the sitcom offers teacher educators and student teachers these kinds of encounters, we provide a reading of three episodes of Schitt’s Creek through a ‘queer utopian’ lens. We accompany this analysis with prompts for teacher educators to use in discussing these episodes in the teacher education classroom. The piece concludes with some thoughts on the significance of comedy for exploring the relationship between affect, education, and social justice more generally

Beyond Pilotitis: Taking Digital Health Interventions to the National Level in China and Uganda

Innovation theory has focused on the adoption of new products or services by individuals and their market-driven diffusion to the population at large. However, major health sector innovations typically emerge from negotiations between diverse stakeholders who compete to impose or at least prioritise their preferred version of that innovation. Thus, while many digital health interventions have succeeded in terms of adoption by a substantial number of providers and patients, they have generally failed to gain the level of acceptance required for their integration into national health systems that would promote sustainability and population-wide application. The area of innovation considered here relates to a growing number of success stories that have created considerable enthusiasm among donors, international agencies, and governments for the potential role of ICTs in transforming weak national health information systems in middle and low income countries. This article uses a case study approach to consider the assumptions, institutional as well as technical, underlying this enthusiasm and explores possible ways in which outcomes might be improved

Structural Evolution of a Bifunctional Mu-Opioid Receptor (MOR)/Delta-Opioid Receptor (DOR) Peptidomimetic as Nonaddictive Opioid Analgesics

Opioids have been used since antiquity for their ability to treat chronic and severe pain. However, their potent analgesic activity comes with severe side effects, including dependence, abuse, and even death by respiratory depression. Since these opioids are unmatched in their ability to treat pain, the development of alternatives without these negative side effects is sorely needed. While numerous strategies have been implemented, none yet have been successful. One promising new strategy involves targeting multiple different opioid receptors at the same time. More specifically, agonism at the µ-opioid receptor (MOR) with simultaneous activity at the δ-opioid receptor (DOR) can attenuate these negative side effects without compromising their analgesic effects. Previously, our lab has synthesized a peptidomimetic series that expresses a MOR-agonist/DOR-antagonist profile. Members of this series were found to express antinociception (a proxy measure for analgesia) in vivo without producing dependence, drug-seeking behavior, or tolerance to the antinociceptive effects. While these effects show great promise, they are only active upon intraperitoneal injection. Since chronic pain requires the administration of drug over a long period of time, enabling oral bioavailability is an important goal to transform these peptidomimetics into nonaddictive analgesics. Unfortunately, these ligands express very poor metabolic stability in mouse liver microsomes (MLM), and this instability is a product of the tetrahydroquinoline core structure of the peptidomimetic. This structure requires numerous synthetic steps to create, and its instability is manifest in several key intermediates. As such, this dissertation describes a series of structure-activity relationship (SAR) campaigns that sought to remove this unstable core while preserving our desired bifunctional opioid activity. Initially, we sought to convert the bicyclic tetrahydroquinoline core of our peptidomimetic series to a monocyclic aromatic core. This immediately resulted in improvements in metabolic stability, and no unstable intermediates were observed. However, the MOR-agonist properties of these ligands, necessary for inducing their analgesic properties, was lost in most analogues in this series, and while a few were better than morphine in vitro, they were not as potent or efficacious as our original peptidomimetics. Using the results of this SAR campaign as a springboard, we next sought to further improve their MOR-agonist properties and metabolic stability. To this end, a series of amine pendants were incorporated onto our monocyclic core analogues. These pendants managed to further improve the metabolic stability of these ligands. It was also discovered that these amines can induce high MOR-efficacy in our peptidomimetics, and when combined with an aromatic ring on the pendant, can induce high MOR-potency. This “aromatic-amine’ pharmacophore was found to produce highly potent and efficacious MOR-agonists, independent of the functionalization of the monocyclic aromatic core. In fact, MOR-superagonists with efficacy of up to 147% compared to the standard MOR-agonist DAMGO were discovered using this pharmacophore, and the pharmacophore even enabled elimination of the aromatic core entirely. All this came with consistent DOR-antagonism or weak partial DOR-agonism, in line with the opioid profile we sought to maintain. Herein, the SAR campaigns that led to the improvement in metabolic stability of these ligands are discussed, as well as the discovery and scope of this aromatic-amine pharmacophore. These campaigns significantly simplified the synthesis of the ligands, yielding no unstable intermediates and enabling a greater degree of structure diversification for future opioid ligands.PHDMedicinal ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/153441/1/seanph_1.pd

Frailty in the critically ill: a novel concept

The concept of frailty has been defined as a multidimensional syndrome characterized by the loss of physical and cognitive reserve that predisposes to the accumulation of deficits and increased vulnerability to adverse events. Frailty is strongly correlated with age, and overlaps with and extends aspects of a patient's disability status (that is, functional limitation) and/or burden of comorbid disease. The frail phenotype has more specifically been characterized by adverse changes to a patient's mobility, muscle mass, nutritional status, strength and endurance. We contend that, in selected circumstances, the critically ill patient may be analogous to the frail geriatric patient. The prevalence of frailty amongst critically ill patients is currently unknown; however, it is probably increasing, based on data showing that the utilization of intensive care unit (ICU) resources by older people is rising. Owing to the theoretical similarities in frailty between geriatric and critically ill patients, this concept may have clinical relevance and may be predictive of outcomes, along with showing important interaction with several factors including illness severity, comorbid disease, and the social and structural environment. We believe studies of frailty in critically ill patients are needed to evaluate how it correlates with outcomes such as survival and quality of life, and how it relates to resource utilization, such as length of mechanical ventilation, ICU stay and duration of hospitalization. We hypothesize that the objective measurement of frailty may provide additional support and reinforcement to clinicians confronted with end-of-life decisions on the appropriateness of ICU support and/or withholding of life-sustaining therapies

Combinatorial Expression Rules of Ion Channel Genes in Juvenile Rat (Rattus norvegicus) Neocortical Neurons

The electrical diversity of neurons arises from the expression of different combinations of ion channels. The gene expression rules governing these combinations are not known. We examined the expression of twenty-six ion channel genes in a broad range of single neocortical neuron cell types. Using expression data from a subset of twenty-six ion channel genes in ten different neocortical neuronal types, classified according to their electrophysiological properties, morphologies and anatomical positions, we first developed an incremental Support Vector Machine (iSVM) model that prioritizes the predictive value of single and combinations of genes for the rest of the expression pattern. With this approach we could predict the expression patterns for the ten neuronal types with an average 10-fold cross validation accuracy of 87% and for a further fourteen neuronal types not used in building the model, with an average accuracy of 75%. The expression of the genes for HCN4, Kv2.2, Kv3.2 and Caβ3 were found to be particularly strong predictors of ion channel gene combinations, while expression of the Kv1.4 and Kv3.3 genes has no predictive value. Using a logic gate analysis, we then extracted a spectrum of observed combinatorial gene expression rules of twenty ion channels in different neocortical neurons. We also show that when applied to a completely random and independent data, the model could not extract any rules and that it is only possible to extract them if the data has consistent expression patterns. This novel strategy can be used for predictive reverse engineering combinatorial expression rules from single-cell data and could help identify candidate transcription regulatory processes

The sardine run : investigating sardine and predator distribution in relation to environmental conditions using GIS and remotely sensed products.

Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2009.The sardine run is a spectacular but poorly understood natural phenomenon. This research aims to broaden scientific knowledge pertaining to sardine, Sardinops sagax, distribution, both in relation to their predators and environmental conditions. Sardine distribution was closely related to sea temperature. Sardines were sighted every year along the Lower Wild Coast, where continental shelf conditions were cooled by the Port Alfred upwelling cell. To the north of Mbashe River, shelf conditions were dominated by the warm Agulhas Current, and sardine distribution varied annually in close relation with sea temperature conditions. Along this coastline sardine abundance always peaked between Waterfall Bluff and Port St Johns with favourable conditions caused by the westward inflection of the coastline and the shelf bathymetry. Topographically-induced upwelling was concluded to be the cause of cooler sea temperatures and elevated chl a concentrations. Although chl a concentration appeared to be associated with east coast sardine distribution, the uncertainty with regards data accuracy hindered their usefulness as a predictor of suitable biological conditions for sardine. Sardine northward movement along the KZN coastline was impeded adjacent to the Durban Eddy, where they were forced shorewards by the warm conditions. This coincided with the peak in beach seine catches. The Cape Gannet, Morus capensis, was very closely associated with sardine along the entire east coast. Their abundance declined substantially adjacent to the Durban Eddy. Prevailing atmospheric conditions affected gannet behaviour: they travelled more frequently during strong alongshore winds and foraged more upon cessation of such winds. Gannets were closely associated with feeding dolphins at both coarse and fine scales, and responded to changes in dolphin behaviour. Common dolphin, Delphinus capensis, abundance and group size peaked between Waterfall Bluff and Port St Johns. Along this stretch of coastline they travelled more slowly, and in pods more perpendicular to the bathymetry of the region. Bottlenose dolphin, Tursiops aduncus, abundance increased during the sardine run with the influx of a migrant stock which reached the KZN Mid South Coast. Humpback Whale, Megaptera novaeangliae, and sardine distributions did not appear to be related