VictorJuiz/thesis huggingface dataset:
The Acute Regulation of Intestinal Chylomicron Secretion by Glucagon-like Peptides

Postprandial overproduction of apolipoprotein B48 (apoB48)-containing lipoproteins has been observed in states of insulin resistance and is important to the sequelae of cardiovascular disease, but little is understood about factors that regulate their secretion. The glucagon-like peptides (GLPs) are released from ileal enteroendocrine L-cells following lipid ingestion. I hypothesized that the GLPs could acutely affect the production of apoB48-containing triglyceride (TG)-rich lipoproteins (TRL) in the small intestine. Using the Syrian golden hamster, I first characterized the gross effects of the GLPs on TRL secretion in response to an oral fat load and then continued to dissect the mechanisms of these changes using primary intestinal cell cultures and a variety of knockout mouse models. An exogenous GLP-1 receptor (GLP-1R) agonist was found to acutely inhibit chylomicron secretion in both hamsters and mouse models, and extending the bioactivity of endogenously-secreted GLP-1 with a dipeptidyl peptidase-4 inhibitor had suppressive effects in insulin-resistant fructose-fed hamsters. The insulinotropic and delayed gastric emptying functions do not completely account for the hypolipidemic effect of GLP-1R agonism, and the effect of the GLP-1R agonist exendin-4 could be seen directly in the apoB48 secretion of primary enterocytes. In contrast, the sister peptide GLP-2 was a potent acute stimulator of chylomicron secretion in hamsters and mice. The hyperlipidemic effect of GLP-2 could be attributed to an increased rate of luminal FA uptake mediated by the posttranslational modification of the FA transporter CD36, and CD36-deficient mice were found to be refractory to the stimulatory effects of GLP-2. The activity of nitric oxide synthase was also found to be essential to the hyperlipidemic action of GLP-2. I identified a set of intercellular communications that could contribute in mediating the action of GLP-2, in which GLP-2 secreted from the enteroendocrine L-cell stimulates intestinal subepithelial myofibroblasts to release vascular endothelial growth factor, which directly activated the enterocyte to secrete apoB48. In summary, this thesis demonstrates that two co-secreted postprandial hormones have considerable but completely opposite influences on chylomicron production. Changing the balance of the GLPs’ actions in vivo could provide a therapeutic strategy to combat postprandial dyslipidemia.

Keywords: apolipoprotein B
insulin resistance
postprandial dyslipidemia
Advisor: Adeli, Khosrow
Teacher Matters: Re-examining the Effects of Grade-3 Test-based Retention Policy

This study is aimed to unpack the ‘black box’ that connects the grade-3 test-based retention policy with students’ academic outcomes. I theorized that the policy effects on teaching and learning may be modified by instructional capacity, but are unlikely to occur through enhancing teachers’ capability to teach. Analyzing the Early Childhood Longitudinal Study Kindergarten cohort (ECLS-K) dataset, I first explored the relationship between the test-based retention policy and instructional capacity as indicated by teacher expectations of students’ learning capability and then investigated whether and how the expectations moderated the policy effects on instructional time reallocation, student academic performance, and student self-perceived academic competence and interests. To remove the selection bias associated with the non-experimental data, I applied a novel propensity score-based causal inference method, the marginal mean weighting through stratification (MMW-S) method and extended it to a causal analysis that approximates a randomization of schools to the test-based retention policy followed by a randomization of classes to teachers with different levels of expectations. Consistent with my theory, I found that the test-based retention policy had no effects on teacher expectations. Although the policy uniformly increased the time allocated to math instruction, it produced no significant changes in students’ overall performance and overall self-perception in math. In addition, I found that students responded differently to the test-based retention policy depending on the expectations they received from the grade-3 teachers. The results suggested some benefits of positive expectations over negative and indifferent expectations in moderating the policy effects, including more access to advanced content, higher learning gains of average-ability students, and more resilient student learning over a long term. However, the results also showed that having positive expectations alone is not sufficient for academic improvement under the high-stakes policy. If implemented by a positive-expectation teacher, the policy could be detrimental to students’ learning in the nontested subject or to their learning of basic reading/math skills. It would as well place the bottom-ability students at a disadvantage. The findings have significant implications for the ongoing high-stakes testing debate, for school improvement under the current accountability reform, and for research of teacher effectiveness.

Keywords: accountability
high-stakes testing
instructional capacity
teacher expectation
student achievement
propensity-score method
Advisor: Hong, Guanglei
A Rough Journey

A Rough Journey is a single movement for orchestra with an approximate length of 14 minutes. The orchestra consists of piccolo, 2 flutes, 2 oboes, 2 clarinets, 2 bassoons, 4 horns, 2 trumpets, 2 tenor trombones, bass trombone, tuba, timpani, percussion (2 players), piano and strings. The piece is inspired by Alfred Schnittke's musical language and features a variety of elements representing different styles. The harmonic language for instance, consists of pure triads (mostly augmented triads) in both tonal and atonal textures, triads with added dissonances as well as clusters. Although for the most part the piece does not follow a traditional harmonic language, I introduce unstable tonal centers occasionally to strengthen the tonal aspect of the music in contrast with its contemporary textures. The composition includes a few monograms as the main thematic materials which include B-A-C-H and D-S-C-H. However, I add extra notes to these motives to make them slightly longer and more unique. For example, I almost always end the B-A-C-H with the starting note, making it B-A-C-H-B. The Shostakovich motive is also extended to DS-C-H-(B flat-A flat-G). These motives are developed and transformed as the piece progresses, and appear with various rhythms. Dodecaphony is another compositional technique which is used in my work. I use "quasi dodecaphonic" rows against other materials as one of the musical layers. Piano is one of the instruments that features this particular technique by playing all twelve notes in a variety of forms. In addition to tone rows with consecutive notes, I also use dodecaphonic approach in a macro level which is a more unique way of using the technique. For example, the first section of the piece features the two discussed main monograms starting from each and every note of all twelve pitch classes, exploring a vast spectrum of notes at the very beginning. At the same time, I make allusions to traditional harmonic progressions by creating triadic structures in this imitative texture. The pivot note F# is introduced against the discussed texture and maintains its prominence throughout the composition. This pivot note serves as the ending point of some sections, including the string introduction.

Keywords: Orchestral movement
Advisor: Chan, Ka Nin
A Measure of Voxel Similarity for Improving the Image-based Quantification of Tissue Structure and Function

Therapeutic response assessment is a key component in adaptive image-guided radiotherapy. Conventional anatomic measures of response offer little information about the spatial distribution of tumor change. Recently developed voxel-wise response assessment methods operating on functional and biological imaging are better capable of evaluating the heterogeneity of response within the tumor, and thus may yield greater sensitivity than conventional approaches. However, voxel-wise analyses are limited by local registration uncertainties inherent to longitudinal imaging of tumors with changing morphology. A multi-resolution local histogram (LH) moment-based measure of voxel similarity was developed for the purpose of assessing the strength of correspondence between voxels of serial tumor images. This measure was first benchmarked through a series of experiments designed to establish robustness to image intensity variation and sensitivity to alterations in tissue structure through application of simulated deformations. The LH similarity method was subsequently developed as a means of mapping the spatial extent of structural change in tumors through the incorporation of an estimate of image complexity. The change maps were applied to a voxel-wise analysis of diffusion-weighted magnetic resonance imaging of patients with glioblastoma, acquired pre- and post-chemoradiotherapy. The sensitivity of the voxel-wise analysis in differentiating responding/stable patients from non-responding/progressing patients was improved by stratifying the analysis voxels according to regions of interest (ROI) based on the LH similarity-based estimate of tumor change. Meaningful correspondence relationships between evaluated voxels are essential for accurate image-based quantification of tumor structure and function with voxel-wise analysis techniques. The LH similarity methods developed here can robustly evaluate the quality of spatial and temporal voxel correspondence relationships and provide an automated tool for ROI selection and voxel change stratification. It is readily extendable to the analysis of the wide array of anatomic, functional and biological imaging currently used to characterize tumors, guide therapy and assess response.

Keywords: image registraton
therapeutic response assessment
magnetic resonance imaging
radiation therapy
voxel-wise analysis
histogram moment
Advisor: Jaffray, David A.
On Cultural Capital: Fine Tuning the Role of Barriers, Timing and Duration of Socialization, and Learning Experiences on Highbrow Musical Participation

Recent research in the sociology of culture has placed significant focus on musical taste and practices. This research agenda has ushered an understanding of the relationship between social class and cultural consumption, and particularly, the implications that patterns of cultural preferences and practices have on social inequality. A frontrunner in this line of work is Bourdieu (1984), who offers a sophisticated and useful theoretical framework—the Cultural Capital Theory—to illuminate the role of culture and its consumption in society. Written as three publishable papers, the chapters use empirical evidence to explore three issues surrounding highbrow musical practices that enrich Bourdieu (1984)’s framework. The first paper (Chapter 2) examines the role of structural and personal barriers in blocking attendance to highbrow concerts. It takes as a starting point Bourdieu (1984)’s argument that upper class individuals are more likely to attend classical music and opera concerts than their lower class counterparts, and questions whether these distinct patterns of participation are attributable to the different barriers that each class faces. The second paper (Chapter 3) offers a sophisticated analysis of the impact of socialization on highbrow concert attendance. By innovatively integrating the concepts of timing and duration, hallmarks the Life Course Perspective, I map out the potentially dynamic nature of the socialization process. In doing so, I illustrate the varying implications that different timing and duration of exposure has on later life highbrow concert participation. The last paper (Chapter 4) investigates the process of socialization to understand what conditions present during this crucial period in time encourage persistence in highbrow musical practices. I find that engaging in interactions that allow one to experience positive emotional resonance, develop a musical identity, and feel a sense of autonomy over musical decisions lead to the propensity to remain engaged in musical activities throughout life.

Keywords: music
culture
education
taste
highbrow
socialization
life course
Advisor: Baumann, Shyon
Wheaton, Blair
The Arctic Polar-night Jet Oscillation

The eastward winds that form each winter in the Arctic stratosphere are intermittently disrupted by planetary-scale waves propagating up from the surface in events known as stratospheric sudden warmings. It is shown here that following roughly half of these sudden warmings, the winds take as long as three months to recover, during which time the polar stratosphere evolves in a robust and predictable fashion. These extended recoveries, termed here Polar-night Jet Oscillation (PJO) events, are relevant to understanding the response of the extratropical troposphere to forcings such as solar variability and climate change. They also represent a possible source of improvement in our ability to predict weather regimes at seasonal timescales. Four projects are reported on here. In the first, the approximation of stratospheric radiative cooling by a linear relaxation is tested and found to hold well enough to diagnose effective damping rates. In the polar night, the rates found are weaker than those typically assumed by simplified modelling studies of the extratropical stratosphere and troposphere. In the second, PJO events are identified and characterized in observations, reanalyses, and a comprehensive chemistry-climate model. Their observed behaviour is reproduced well in the model. Their duration correlates with the depth in the stratosphere to which the disruption descends, and is associated with the strong suppression of further planetary wave propagation into the vortex. In the third, the response of the zonal mean winds and temperatures to the eddy-driven torques that occur during PJO events is studied. The collapse of planetary waves following the initial warming permits radiative processes to dominate. The weak radiative damping rates diagnosed in the first project are required to capture the redistribution of angular momentum responsible for the circulation anomalies. In the final project, these damping rates are imposed in a simplified model of the coupled stratosphere and troposphere. The weaker damping is found to change the warmings generated by the model to be more PJO-like in character. Planetary waves in this case collapse following the warmings, confirming the dual role of the suppression of wave driving and extended radiative timescales in determining the behaviour of PJO events.

Keywords: climate variability
seasonal forecasting
polar vortex
stratospheric sudden warmings
radiative transfer
stratosphere-troposphere coupling
annular modes
general circulation
Advisor: Shepherd, Theodore G.
Digital Short Fiction and its Social Networks

This thesis considers how the digital medium and social networks affect the short story. I argue that digital short fiction has shown changes, such as signs of becoming more modular or briefer than its print counterparts, and that it has also reflected a shift to the personal or semi-autobiographical story. Digital short fiction has also been used increasingly to market a publisher’s or author’s name or non-digital works. I begin contextualizing this shift in Chapter 1 by analyzing different approaches to the study of the short story, including an overview of generic and historical scholarship, and I conclude with a working definition of the short story. In Chapter 2, I analyze early digital short fiction along with the themes of contemporary fiction in general that have been affected by digital media, social networks, and other changes. I also consider digital short fiction in the context of its publication media, postmodernism, and changes in communication in general. In Chapter 3, I verify these considerations with responses to questionnaires sent to writers of short fiction both on the Web and off. By studying these writers’ conceptions of the short story, preferred publication media, and writing habits, I build on the working definitions of the short story from Chapters 1 and 2. In Chapter 4, I consider the effects on the short story and conclude that we can update print-based conceptions of the short story to include born-digital short fiction and accommodate the contemporary shift in general to modularity, open source, social networks, and the focus on the self. Rather than establishing a concrete definition of what short fiction is at this time, I conclude that a better approach is to replace pre-defined categories with an acknowledgement that the short story is perhaps shifting closer to pre-print storytelling roots, although within the confines of current limitations such as copyright and the attention span of contemporary readers. Although we cannot fully quantify these changes at this time, I argue that they impact the short story and require scholars to consider its paratexts and publication media differently than in pre-Web years.

Keywords: digital literature
short story
electronic literature
born-digital fiction
short fiction
writing communities
Advisor: Lancashire, Ian
Host Pathogen Interactions in Malaria and Tuberculosis: Experimental Models and Translation to Novel Adjunctive Therapies

Malaria and tuberculosis together account for more than 2 million deaths worldwide each year. The present body of work examines interactions between these leading pathogens and cross-cutting themes in innate immunity to both diseases. Not only are malaria and tuberculosis important threats to public health in their own right, but malaria-tuberculosis co-infection appears to generate more severe pathology than either disease on its own, and malaria may exacerbate primary or re-activation tuberculosis (Chapter 2). Moreover, both diseases appear to share common host defense pathways, including CD36, a macrophage cell surface receptor important for innate immunity (Chapter 3). Biomarkers of host defense pathways common to both malaria and tuberculosis distinguish between clinical disease phenotypes and predict mortality in severe malaria (Chapters 4-7). Biomarker discovery led to the identification of angiopoitetin-2 (Ang-2) as a surrogate marker of disease severity in malaria and a potential therapeutic target. Nitric oxide, in addition to its antimycobacterial properties, is known to inhibit Ang-2 release from the endothelium, and is therefore hypothesized to improve outcomes in African children with severe malaria (Chapters 8 and 9). A broad range of methods are applied to address these diseases and their interactions, ranging from mammalian cell culture experiments in vitro, animal models of disease, analysis of human samples, and clinical epidemiology (randomized controlled trial). Translational aspects of this research are emphasized, outlining how advances in understanding of infectious disease pathogenesis can be applied to improved diagnosis, prognosis, and novel adjunctive therapies for two of the leading global infectious threats.

Keywords: malaria
tuberculosis
Advisor: Kain, Kevin C.
Evidence for a Dynamic Adaptor Complex between the P1 Plasmid and Bacterial Nucleoid Promoted by ParA and ParB Partition Proteins

P1 prophage is stably maintained in E. coli as a low-copy-number plasmid. Stable maintenance of P1 is dependent on the function of the plasmid encoded partition system, parABS. ParA is the partition ATPase, ParB is the partition-site binding protein, and parS is the partition site. The concerted action of these proteins results in dynamic movement of the plasmid over the bacterial nucleoid, which results in its stable maintenance. Plasmid movement has been proposed to be caused by interactions between parS bound ParB and nucleoid bound ParA. In this thesis, I have identified a complex of ParA, ParB, and DNA that is capable of promoting plasmid stability. ParA, ParB, DNA interactions required the ATP bound conformation of ParA. The ParA-ParB-DNA complex was dynamically regulated by nucleotide hydrolysis, which promoted complex disassembly. Complex formation resulted from the cooperative binding of ParA and ParB to DNA. ParA-ParB and ParB-DNA interactions were both necessary for complex formation. ParA-ParB-DNA complex size was regulated by ParB stimulation of ParA-ATP hydrolysis. Microscopy demonstrated that complexes resulted in the association of multiple DNA molecules due to protein binding. The properties of complex assembly, dynamics, and DNA grouping lead me to propose a model where associations between ParA bound to the bacterial nucleoid and the partition complex mediated plasmid movement and localization.

Keywords: Chromosome Dynamics
Plasmid Partition
ParA
ParB
P1
Low-copy-number plasmid
Nucleoid-adaptor complex
NAC
Advisor: Funnell, Barbara E.
British Intelligence and Turkish Arabia: Strategy, Diplomacy, and Empire, 1898-1918

This dissertation addresses early British intelligence activities and Anglo-Ottoman relations by viewing the activities of army officers and private individuals as a collective pursuit to safeguard British imperial interests. It offers a new understanding of the relationships between intelligence, grand strategy, and diplomacy before the Great War. It also examines the role that pre-1914 intelligence played in that conflict. The Boer War had shown that the geographic expanse of the British Empire was a source of strategic danger as well as a foundation of global power. The revelation of weakness propelled Britain to begin collecting intelligence on possible sources of conflict in preparation for the next war. A 1906 border incident between Egypt and Turkey marked turning points in Anglo-Ottoman relations and British intelligence efforts. Intelligence began to focus on railways that threatened Britain’s commercial position, on the disposition of Arab tribes who might revolt against Turkish authority, on the state of the Turkish army, and on the extent of European activity in Turkey. In 1914, British policy in the Middle East was unco-ordinated. Needing an effective means of combatting the Turco-German Jihad proclaimed in 1915, London created the Arab Bureau as an advisory organ based in Cairo. It became the central repository for much of the intelligence gathered before 1914. Officials in Cairo and London created new maps, compiled route reports, and assembled intelligence handbooks for distribution. Once the Arab Revolt began in 1916, intelligence helped marshal Britain’s resources effectively in pursuit of victory. Placing pre-1914 intelligence in the context of British imperial concerns extends our understanding of Anglo-Ottoman relations by considering strategic and diplomatic issues within a single frame. It demonstrates the influence of the Boer War in initiating intelligence-gathering missions in the Ottoman Empire, showing that even those undertaken before the establishment of a professional intelligence service in 1909, although lacking organization, were surprisingly modern, and ultimately successful. Analysis of under-utilized sources, such as the handbooks created by the Arab Bureau and the Royal Geographical Society, demonstrates the value of pre-war intelligence in detailed ways. It deepens understanding of the role British intelligence played in the defeat of the Ottoman Empire and shows how one nation’s intelligence, military, and diplomatic bodies operated separately and collectively in an era that presented them with unprecedented challenges and opportunities.

Keywords: History
Intelligence
Great Britain
Arabia
First World War
Ottoman Empire
Diplomacy
Empire
Advisor: Retallack, James