Background: Obesity has a strong correlation with the development of type two diabetes. As adipocytes accrue in obesity, adipose tissue may induce peripheral insulin resistance through production of pro-inflammatory cytokines and unregulated lipolysis after stimulation by endotoxin or environmental cues. In addition, obesity poses high risks of Staphylococcal aureus colonization and infection. S. aureus can cause a myriad of serious illnesses in both immunocompromised and healthy individuals. Among the S. aureus virulence factors, superantigens are essential for the organism's pathogenesis. Considering the importance of the microbiome in human illnesses, we've examined whether a staphylococcal superantigen has an impact on the development of type two diabetes via affecting adipocytes. Methodology/Principal Findings: Immortalized human adipocytes and primary rabbit adipocytes that were exposed to staphylococcal superantigen toxic shock syndrome toxin-1 (TSST-1), stimulated proinflammatory cytokine and chemokine production, and such effect could be significantly enhanced by endotoxin and other proinflammatory signals. TSST-1 also induced lipolysis in both human and rabbit adipocytes. Prolonged treatment of rabbits with subclinical doses of TSST-1 induced chronic systemic inflammation and an increase in circulating endotoxin levels, which ultimately resulted in adipocyte insulin resistance and systemic impaired glucose intolerance. Conclusions/Significance: Endotoxin has been proposed to contribute to type two diabetes through enhanced insulin resistance after chronic exposure and stimulation of adipocytes to produce cytokines. Our data indicate that staphylococcal superantigen(s) can also induce proinflammatory cytokine production and lipolysis in adipocytes. In addition, rabbits, which are chronically exposed to superantigens, experience asymptomatic systemic inflammation, high circulating endotoxin levels, and glucose metabolism deficiency that are common symptoms observed in type two diabetic patients. This is the first study that has shown that bacterial exotoxins, like S. aureus superantigen, may directly contribute to the development of type two diabetes.

The purpose of this research is to provide information about the psychometric properties of technology-enhanced (TE) items and the effects these items have on the content validity of an assessment. Specifically, this research investigated the impact that the inclusion of TE items has on the construct of a mathematics test, the technical properties of these items, and the influence these item types have on test characteristics. An empirical dataset was used to investigate the impact of including TE items on a multiple-choice (MC) assessment. The test used was the Iowa End-of-Course Algebra I (IEOC-A) assessment. The sample included 3850 students from the state of Iowa who took the IEOC-A assessment in the spring of 2012. The base form of the Algebra EOC assessment consisted of 30 MC items. Sixty TE items were developed and aligned to the same blueprint as the MC items. These items were appended in sets of five to the base form, in effect resulting in 12 different test forms. The forms were randomly assigned to students during the spring administration window. Several methods were used in an attempt to form a more complete understanding of the content characteristics and technical properties of TE items. This research first examined whether adding TE items to an established MC exam had an effect on the construct of the test. The factor analysis confirmed a two-factor model comprising latent factors of MC and TE items, indicating that TE items may add a new dimension to the test. Subsequent to these findings, a more thorough analysis of the item pool was conducted and IRT analyses were done to investigate item information, test information, and relative efficiency. This analysis indicated that there may be a difference in the way students perform on MC and TE items. There is evidence in this particular pool of items that there is a difference in these two item types. This difference may manifest itself as an additional, perhaps unintended, construct on the exam. Additionally, TE items may perform differently depending on the ability level of the student. Specifically, TE items may provide more information, and measure the construct more efficiently than MC items at higher levels of ability. Finally, the quantity of TE items included on a test has the potential to affect the relative efficiency of the instrument, underscoring the importance of selecting items that reinforce the purpose and uses of the test.

This collection of work grew from a guided journey and an exploration of ideas that has not only encouraged my growth as an artist, but as a responsible citizen sharing this world with others. Over the duration of this evolution I have become increasingly attentive to what I feel is our collective manufactured existence; the things that we produce and the influence that this production has on our lives. From the built environment, material and immaterial commodities, advertising and marketing, consumption, sustainability, etc., all these continuously shifting factors act as constants in our lives and shape our psychosocial development. To better understand this, I have delved into looking at both myself and others for evidence of the various effects from living in a consumer culture. Drawing also from extensive research in the history of as well as contemporary theories on production, mass media culture, addiction, exploitation of people and resources, and the growth of technology, I look to increase not only my own awareness on these subjects, but to also educate others. My process of making work is a meditation in order to better facilitate inspection intertwined with introspection. A finished piece becomes an externalization of this effort, but not as a conclusion. The various mixed media included in All These Things is the culmination of an ongoing search that encourages conversation and further evaluation of our roles in a commodity culture. By coming at this multi-faceted topic from different directions, I am offering a radial view into the many possible considerations for what it means to be a consumer and how this affects us all.

The interplay between cancer cells and the extracellular matrix (ECM) remains a critical regulator of both normal tissue organization and cancer cell invasion. Proteins that function as ECM receptors function to link the cell with the ECM. Abberations in either the structure of the ECM or the expression of ECM receptors leads to disrupted interaction and downstream signaling effects. Dystroglyan (DG) is an ECM receptor that is expressed in a variety of tissue types and functions to mediate sarcolemma stability, epithelial polarity, and is critical in the early formation of basement membranes. However, DG has primarily been studied in muscle where loss of its function is linked to a host of muscular dystrophies. In the epithelium, the role of DG remains enigmatic. While DG has repeatedly been shown to lose function during cancer development and progression, the mechanism and functional consequence of its loss are currently unknown. In order to increase our understanding of DG in cancer development, we analyzed its expression and glycosylation, a functional requirement for DG, in a range of prostate cancer cell lines. Previous work has shown DG to be downregulated in prostate cancer, but the mechanism by which this occurs has remained largely unclear. We found that DG expression is maintained while its glycosylation was heterogeneous in the cell lines. Further investigation revealed that lines with hypoglycosylated DG strongly associated with the loss of expression of the glycosyltransferase LARGE2. Further this enzyme is frequently downregulated in human cancers and appears to serve as a required enzyme in DG glycosylation within prostate epithelium. This is the first work to demonstrate the functional requirement of LARGE2 for DG, and the only work to implicate loss-of-function of LARGE2 in cancer progression. To determine whether loss of LARGE2 is found in other tumor types, we analyzed human clear cell renal cell carcinoma (ccRCC) samples by immunohistochemistry and via in silico analysis with the Cancer Genome Atlas (TCGA). Our work demonstrated a frequent and significant downregulation of LARGE2 expression and its association with DG hypoglycosylation. Additionally, we found the loss of LARGE2 strongly associated with increased mortality. Thus, we again demonstrated a functional requirement of LARGE2 but also found a clinical correlate with increased mortality. Finally, we examined the functional outcome of DG hypoglycosylation or loss of expression in both a mouse model of prostate cancer and a variety of cell lines models. We found that while loss of DG expression does not increase prostate cancer growth or metastasis in one model of cancer, loss of its glycosylation does seem to mediate downstream metabolic changes within cells. The mechanism for this change remains unclear. In summary, these studies have contributed to our understanding of DG glycosylation and function in both prostate and renal carcinoma. Additionally, we have shown a novel mechanism by which DG glycosylation is lost with downregulation of LARGE2 expression. Finally, while we were unable to demonstrate a clear mechanism by which signaling changes arose, we were able to demonstrate a strong correlation between DG hypoglycosylation and increased mortality in ccRCC. These insights could be used to improve treatment of multiple cancer types as our understanding of DG function continues to improve.

Ananda Devi [1957 - ], a French-language author and poet from Mauritius, adds depth to the lyricism already inherent in her writing by drawing upon that country's multicultural heritage, which includes African, Hindu, and French, and its Creole language. Le Long Désir (2003) defies genre, being neither strictly poetry nor prose, and presents more a collection of prose poems than a structured story with a tangible plot. The poetic aspect of her text, accomplished through this Creole as well as experimentation with grammatical structures and the display of the text on the page, inclines me as a translator to prioritize the lyricism of her text over its content, though cer-tainly I have endeavored to bring both into my English translation of selected sections of the book. Its unifying theme of the struggle of women with violence, anguish and self-definition is brought to the fore by running motifs of animalistic behavior, putrefaction, and darkness, which are accompanied by equally vivid instances of fragility and beauty, signaling the plurality of the situation of women. The challenges of translating the Creole, of preserving her imagery's fresh-ness as well as the content's poignancy, and other myriad deliberations make the labor of produc-ing The Long Desire, the English translation, that much more rewarding; for it is well worth bringing a glimpse of life as a Mauritienne to an English-speaking audience, if not for the noble purpose of increasing our awareness of the world, then at least to taste the enchanting complexity of the text itself.

When most omnivores and herbivores become sodium depleted they engage in the motivated behavior of sodium appetite (AKA salt appetite), or the seeking out and ingestion of salty substances. Sodium appetite is associated with psychological processes that serve to enhance the incentive and rewarding value of salty substances in order to attract animals to salty substances and reinforce the ingestion of them. The experience of sodium depletion also produces long-lasting changes in behavior; one of the most apparent changes being a seemingly life-long increase in hypertonic salt intake which indicates sodium appetite is sensitized. Two neural circuits have been implicated in the sensitization of sodium appetite: 1) a forebrain neural circuit that regulates body fluid homeostasis, and 2) the mesolimbic dopamine system which mediates motivated behaviors. This dissertation has three aims that serve the overall purpose of providing a better understanding of the neurobiological mechanisms that mediate the sensitization of sodium appetite. The first aim is to develop a model of sodium depletion that is amenable to pharmacological manipulation in order to determine whether the -blockade of N-methyl-d-aspartate receptors, which are critical for neural plasticity, will prevent the sensitization of sodium appetite. The second aim is to determine whether sensitization is associated with relatively long-term molecular changes in forebrain areas that regulate body fluid homeostasis. The third aim is to identify how forebrain areas involved in body fluid homeostasis may connect to and influence activity in the mesolimbic dopamine system.

Introduction: Velopharyngeal inadequacy (VPI) may result in inappropriate oral/nasal coupling during the production of speech sounds, resulting in unwanted nasal resonance and/or nasal air emission. Orthognathic surgeries such as maxillary and/or mandibular advancements are also known to change skeletal and muscular structures resulting in changes affecting velopharyngeal closure (VPC). Although many studies have reported on the effect of maxillary advancement surgery on VPI for patients with cleft lip and palate, the effect of mandibular advancement on VPI has not been studied at length. The purpose of this study was to elucidate the effect of temporary prosthetic mandibular advancement on velopharyngeal function. Methods: Fourteen subjects (7 males, 7 females) with no history of craniofacial abnormalities or speech disorders were recruited. The mean age was 35 years (range = 26-60). Acoustic nasalance measurements were obtained during nasal sentences and during sentences without nasal consonants in two conditions; normally, and while wearing an elastic mandibular advancement (EMA) appliance to advance the mandible by 13mm. In addition, subjects were asked to produce five repetitions of the sentence "Ten men came in when Jane left" while recordings were obtained with a videoendoscopy/phototransducer system that sensed the amount of light passing through the velopharyngeal orifice. The endoscope and fiber optic light were inserted through the subject's middle nasal meatus and positioned above the velum. The phototransducer fiber was extended through the velopharyngeal port into the upper oropharynx to detect light passing through the orifice as the velopharyngeal mechanism opened and closed. Individual subject's outcomes with and without the EMA appliance were analyzed statistically using paired t-test for Nasalance test, and one-way ANOVA/independent samples t-test for phototransducer test. Results: Nasalance did not deteriorate, but significantly decreased for the ‘nasal’ sentences after mandibular advancement, whereas changes in nasalance were not significant for the sentences containing no nasal consonants after mandibular advancement. Mandibular advancement by a 13 mm using an EMA appliance did not significantly affect VPC. Instead, large variability among subjects in response to mandibular advancement. For 7 of the 14 subjects, the extent of VPC decreased significantly (p < .05) under the advanced mandible condition compared to the normal condition (without the EMA appliance). On the other hand, 5 subjects showed significantly (p < .05) increased VPC when their mandibles were advanced. For 2 subjects, VPC was not significantly changed with the advanced mandible. Conclusions: The outcomes of this study suggested that there was no statistical evidence to support that nasality was deteriorated by a 13mm mandibular advancement, which agreed with recent studies describing velopharyngeal function and nasality after orthognathic surgeries. VPC was not affected by mandibular advancement. Responses of the nasalance and VPC to mandibular advancement were dependent on the individuals. Further investigation such as electromyography method is needed to understand how velopharyngeal function and speech respond to mandibular advancement more definitely.

The retinal vasculature analysis plays an important role in the diagnosis of ophthalmological diseases, as well as general human disorders that manifest on the retina. The fundus photograph is a 2-D color image modality of the retina and is widely used in modern ophthalmology clinics due to its relatively low cost and its non-invasive access to the retina. However, due to the complexity of the retinal vasculature presented on the image and the large variation of the image quality, no automated method is able to re-construct the retinal vasculature (i.e. construct arteriovenous trees) satisfactorily, thus preventing its analysis on large-scale clinical datasets. In this thesis, we present a systematic and complete study to automatically construct the retinal vasculature on fundus photographs and apply it to a clinical dataset. First of all, a preliminary study is conducted to detect and classify important landmarks in the retinal vasculature using a machine learning method. The evaluation of this method reveals the difficulty of identifying each landmark as an independent target. Then a novel and more global method is proposed to construct retinal arteriovenous trees (A/V trees). The strategy of the proposed method is to build an over-connected vessel network, and separate it into vascular trees, then classify them into A/V trees. Particularly, by taking advantages of specific properties of the retinal vasculature, global and local information are combined together to recognize landmarks of the vasculature. Instead of recognizing each landmark independently as other methods do, this method considers the relationship between landmarks in a more global manner, thus recognizing them simultaneously and globally. With a special graph design, each landmark is associated with multiple possible configurations and costs, and a near optimal solution is selected by minimizing the costs of landmarks and the global property of the whole vascular network. With each landmark recognized, the A/V trees are easily inferred with a pixel classification method. By doing so, local noise in the images and local errors during pre-processing are corrected to some degree, and small vessels that are difficult to classify locally can also be recognized. The proposed method is compared with another method and the evaluation demonstrates its superiority. To demonstrate its potential applicability, we apply the proposed method on a cohort study data of HIV-infected patients with treatment. New metrics to analyze retinal vessel width is developed based on the A/V trees built using the proposed method, and it is compared with a conventional metric. Statistical analysis reveals the advantages of the new metric and thus indicates the benefit of the proposed method and its potential application on large datasets.

Sunset Iridescence is a one of a kind sculptural bookwork which reflects the essence of the wings of the Madagascar Sunset Moth. My work is very much about the physical qualities of the materials I use. The papers, inks and gilding supplies used to recreate the colors and iridescence of the moth are described. A comparison of color created by pigment and color created by the refraction of light rays is discussed. Parallels are drawn between the structure of the codex and the behavioral patterns of the moths. The local name for the Madagascar Sunset Moth is Lolonandriana - lolo for `spirit or soul,' andriana for `noble.' I was inspired by this concept of the soul to publish a letterpress printed chapbook. Unlike Flying in an Airplane is a short memoir of one of my experiences as a flight nurse. It recalls the first moments of lifting off in a helicopter as I prepared to stabilize and transport a critically ill child.

Galen's Avoiding Distress provides an opportunity for scholars to qualify Galen's philosophical eclecticism because his ἄσκησις to avoid distress intersects theory and practice. My thesis carefully analyzes the theoretical framework behind Galen's claim that he “trained his φαντασἰαι for the loss of all his possessions” as well as the specific practices that constitute this training regimen. I trace the concept of φαντασἰα back to the first philosophical discussions in Plato's Theaetetus-Sophist structure and Aristotle's De anima to answer the questions “What are the φαντασἰαι that he talks about?” and “How do they participate in cognition?” I analyze Galen's On the doctrines of Hippocrates and Plato, Affections and Errors, and Thrasybulus to identify Galen's specific practices and relate them to what Galen thinks is the purpose of all humans. My inquiry allows me to argue that while Galen uses his imagination to condition himself not to fear the atrocities of Commodus he subordinates emotional tranquility and practices that promote it to the greater goal of doing good deeds for others.