VictorJuiz/thesis huggingface dataset:
Intestinal Cholecystokinin and Leptin Signaling and the Regulation of Glucose Production
Keywords: Bypass Surgery
Cholecystokinin
Diabetes
Glucose production
Leptin
Obesity

The number of individuals affected by diabetes is on the rise due in part to lifestyle and/or genetic factors. Diabetes and obesity are characterized by a disruption in glucose homeostasis due in part to an elevation in glucose production (GP). It is of utmost importance to understand the regulation of GP in normal, obese and diabetic settings in hopes to unveil therapeutic targets that lower blood glucose concentrations in diabetes and obesity. The small intestine has also been documented to regulate glucose homeostasis independent of changes in food intake although the intestinal signaling mechanism(s) remain largely unknown. Specifically, the duodenum senses an increase in lipids and triggers release of CCK and activates the CCK1 receptor in the duodenum to lower GP via a gut-brain-liver axis. However, the downstream intestinal CCK1 receptor signaling effectors remain unknown. In study 1 of this thesis, the signaling molecule PKA was shown, for the first time to our knowledge, to lie downstream of the duodenal CCK1 receptor to trigger vagal afferent firing and a gut-brain-liver axis to lower GP. Importantly, direct activation of duodenal PKA lowered GP and bypassed duodenal CCK resistance in high fat fed rats. Like the duodenum, the distal part of the small intestine, the jejunum, also senses lipids to lower GP via a gut-brain-liver axis, but whether hormonal action mediates this GP-lowering effect of the jejunum remains unknown. In study 2 of this thesis, a novel GP-lowering effect of leptin in the jejunum was described. Specifically, jejunal leptin activated the long form leptin receptor and PI3K to lower GP in normal, high fat fed or uncontrolled diabetic rodents via a neuronal network, and contributed to the early anti-diabetic effect of bariatric surgery. In conclusion, this doctoral thesis demonstrates that independent activation of duodenal CCK-PKA and jejunal leptin-PI3K signaling potently lowers GP in normal, high-fat fed and diabetic rodents via a gut-brain-liver neuronal axis. Thus, targeting hormonal (i.e., CCK and leptin) signaling in the small intestine represents a potential therapeutic strategy to lower GP and restore glucose homeostasis in diabetes and obesity, and may mimic the anti-diabetic effect of bariatric surgery.
High Performance Spatial and Spatio-temporal Data Processing
Keywords: Indexing
LBS
Moving object trajectory
Spatial
Spatial join
Spatio-temporal

The rapid growth of spatial data volume and technological trends in storage capacity and processing power are fueling many emerging spatial and spatio-temporal applications from a wide range of domains. Spatial join is at the heart of many of the emerging spatial data analysis applications. However, spatial join processing on even a moderate sized dataset is very time consuming. At the same time, there is a rapid expansion in available processing cores, through multicore machines and Cloud computing. The confluence of these trends points to a need for effective parallelization of spatial query processing. Unfortunately, traditional parallel spatial databases are ill-equipped to deal with the performance heterogeneity that is common in the Cloud. We introduce a parallel spatial data analysis infrastructure that exploits all available cores in a heterogeneous cluster. We also present an approach to parallelize spatial join queries in a large main memory multicore machine. Among the emerging spatio-temporal applications Location Based Services (LBS) are the most prominent. These applications are characterized by high rate of updates and many concurrent short running range queries. We present a parallel in-memory spatio-temporal indexing technique to support the demands of LBS workloads. Our system achieves significantly better performance than existing approaches to indexing spatio-temporal data. We also introduce a parallel in-memory spatio-temporal topological join approach.
Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways
Keywords: body-weight
GlcNAc
Hexosamine
metabolism
Mgat5
N-glycan branching

Most mammalian growth factor receptors and solute transporters are co-translationally N-glycosylated. N-glycans are branched and elongated in the Golgi, and their interaction with lectins regulates cell surface residency and activity of transmembrane glycoproteins. The Golgi branching N-acetylglucosaminyltransferases, Mgat1, 2, 4, 5 and 6, require a common donor substrate uridine-diphosphate-N-acetylglucosamine (UDP-GlcNAc) generated de novo by the hexosamine biosynthetic pathway (HBP) from glucose, glutamine and acetyl-CoA, as well as from GlcNAc salvage pathway. In this thesis I describe evidence for cell-autonomous regulation of cellular metabolism by the Golgi N-glycan branching pathway. Induced expression of Mgat1, Mgat5 or Mgat6, and GlcNAc supplementation to the HBP, increased central metabolites in an additive manner. I show that UDP-GlcNAc levels are also sensitive to dietary GlcNAc supplementation in vivo, increasing nutrient uptake and promoting anabolic metabolism via the Golgi N-glycan branching pathway. Chronic oral GlcNAc supplementation in C57BL/6 mice increased hepatic UDP-GlcNAc and N-glycan branching on liver glycoproteins. Furthermore, GlcNAc supplementation altered levels of numerous hepatic metabolites, insulin and glucagon balance, and promoted excess lipid storage, as well as body-weight increase, without affecting food intake or energy expenditure. In cultured cells, GlcNAc enhanced uptake of glucose, glutamine and fatty acids, and elevated fatty acid synthesis and storage in an N-glycan-dependent manner. Mgat5-/- mice exhibit a lean phenotype, and oral GlcNAc rescued fat accumulation, consistent with functional redundancy of N-glycan branches. However, fat accumulation in this context was rescued at the expense of lean mass, suggesting that Mgat5 plays a role in lean to fat body composition. These results suggest that GlcNAc reprograms cellular metabolism by enhancing nutrient uptake and lipid storage through the HBP and UDP-GlcNAc supply to the Golgi N-glycan branching pathway.
Making a Scene: Producing Media Literacy Narratives in Canada
Keywords: Media Education
Media Literacy
Media Studies
Scenes
School Subjects

In a highly mediated world, understanding how we communicate becomes an essential skill of citizenship. In Canadian secondary schools this is often taught as media literacy, either as a new stand-alone subject or integrated within the existing curriculum. As a school subject media literacy is particularly difficult to define and document because it continually changes to keep pace with technological innovation. Combining aspects of genealogy and scene-based analysis helps attend to the spatial and temporal formations of media literacy, thus bringing principles of circulation, exchange, and ephemerality into view. The first part of this dissertation considers the construction of media literacy as a secondary school subject in Canada. I problematize the dominance of a single historical narrative, where Ontario has come to stand in for the rest of the country, by tracing that narrative’s genealogical threads any by considering how it has travelled both nationally and internationally. I argue that a multitude of narratives have been obscured by this singular version of events. In the second part of the dissertation I study one such alternative narrative in British Columbia, using the sensitizing concept of “scene” to better understand how school subjects are produced. The various places, actors, organizations and activities producing a media literacy scene in BC do not neatly fit into the dominant national narrative. I discuss some of the ways in which school subjects have been studies, and then advance a model of scene-based analysis as a more flexible, generative research framework for studying social phenomena. I argue that media literacy is more than just a collection of canonical theories and methods. Its specific formation is contingent upon and shaped by forces both inside and outside of institutional learning, influenced by national and transnational trends, as well as locally specific conditions and relations.
Nonlinear Polarimetric Microscopy for Biomedical Imaging
Keywords: Biomedical Imaging
Nonlinear Optics
Polarization
Stokes Mueller Polarimetry

A framework for the nonlinear optical polarimetry and polarimetric microscopy is developed. Mathematical equations are derived in terms of linear and nonlinear Stokes Mueller formalism, which comprehensively characterize the polarization properties of the incoming and outgoing radiations, and provide structural information about the organization of the investigated materials. The algebraic formalism developed in this thesis simplifies many predictions for a nonlinear polarimetry study and provides an intuitive understanding of various polarization properties for radiations and the intervening medium. For polarimetric microscopy experiments, a custom fast-scanning differential polarization microscope is developed, which is also capable of real-time three-dimensional imaging. The setup is equipped with a pair of high-speed resonant and galvanometric scanning mirrors, and supplemented by advanced adaptive optics and data acquisition modules. The scanning mirrors when combined with the adaptive optics deformable mirror enable fast 3D imaging. Deformable membrane mirrors and genetic algorithm optimization routines are employed to improve the imaging conditions including correcting the optical aberrations, maximizing signal intensities, and minimizing point-spread-functions of the focal volume. A field-programmable-gate array (FPGA) chip is exploited to rapidly acquire and process the multidimensional data. Using the nonlinear optical polarimetry framework and the home-built polarization microscope, a few biologically important tissues are measured and analyzed to gain insight as to their structure and dynamics. The structure and distribution of muscle sarcomere myosins, connective tissue collagen, carbohydrate-rich starch, and fruit fly eye retinal molecules are characterized with revealing polarization studies. In each case, using the theoretical framework, polarization sensitive data are analyzed to decipher the molecular orientations and nonlinear optical susceptibilities. The developed nonlinear optical polarimetric microscopy is applicable to a wide variety of structural studies on ordered materials, and provides a non-invasive possibility to study the structural organization and dynamics within biological samples. For example, the technique is well suited for studies of a muscle contraction, histopathology of collagen structure for cancer tissue diagnostics, investigations of the polysacharide structural organization within a starch granule of a plant, or developmental study of the retina in an eye, among other applications.
Adiposity and Brain Health: A Study of Adolescents and Middle-aged Adults
Keywords: adolescence
brain
cognition
fat mass
obesity
visceral fat

Obesity, the excess accumulation of adipose tissue, presents a substantial public health burden. Research emerging over the past decade has shown that midlife obesity is associated with altered brain structure and increased risk of developing dementia. Prior research examining obesity-brain health relationships have utilized anthropometric measures of obesity (such as body mass index) and focused on adult populations. The current research aims to build on our understanding of obesity-brain health relationships by a) moving beyond the limitation of body mass index to examine the unique contributions of visceral vs. peripheral adiposity and b) examining two populations: adolescents and middle-aged adults to gain a clearer understanding of how these relationships progress across the lifespan. To this end, four investigations of obesity-brain health relationships were conducted. First, the relationship between adiposity and cognitive performance was examined in adolescents, and revealed a negative association between visceral fat and executive functioning that was more pronounced in females than in males. Second, the relationships between adiposity and two measures of structural brain integrity, signal intensity and magnetization transfer ratio, were assessed in adolescents. Robust relationships were found, possibly indicating variations in membrane phospholipid composition. Third, the relationship between adiposity and cortical thickness was examined in adolescents, revealing age-moderated relationships between adiposity and cortical thickness in males. Fourth, the relationships between adiposity and brain volumes, white matter integrity and cognition were examined in middle-aged adults, demonstrating a negative relationship between adiposity and brain volumes, as well as measures of white matter integrity. Overall these results suggest that high adiposity in adolescents is associated with altered brain structure and cognition, while in middle-aged adults, high adiposity is associated with altered brain structure. Given the rising rates of obesity worldwide, this research has implications for brain health throughout the lifespan.
Coverage Analysis and Resource Allocation in Heterogeneous Networks
Keywords: Coverage Analysis
Heterogeneous Networks
Poisson Point Process
Resource Allocation
Stochastic Geometry
Wireless Communications

The focus of this thesis is the analysis and design of multi-tier heterogenous networks (HetNets) with large density of access points (APs) located without a deterministic structure. We use stochastic geometry, specifically Poisson point processes (PPPs), to capture the randomness in AP locations. To differentiate their structural characteristics, APs are categorized into different tiers, each modeled by a PPP. The problem of cell association and resource allocation in a HetNet is considered from two different points of view: when the user is i) mobile and ii) stationary. To incorporate mobility in coverage analysis for mobile users, we derive the probability of handoff in an irregular multi-tier HetNet. To account for the service degradation due to handoffs, we propose a linear cost function, and use this to associate high speed users to upper tiers (e.g., macrocells) with a lower AP density. For stationary users, we first derive the statistical distribution of the load, and the minimum bandwidth required to meet an outage constraint in a multi-tier HetNet. This result is most useful for system design by relating the required spectrum to choices of network parameters. We then consider the dual problem with the objective of maximizing the overall rate coverage with orthogonal spectrum allocation across tiers given a total available bandwidth. We tackle this problem in two different phases: 1) load distribution and spectrum partitioning across tiers; 2) resource allocation across the APs and users within one tier. For analytical tractability in the former, we approximate the load of each AP by its mean, and derive the optimum tier association and fraction of spectrum to be allocated to each tier. In the latter, to account for different loads at each AP, we develop a hierarchical algorithm to allocate the available spectrum across the APs according to their load and to users according to their data rate demand. The latter benefits from adaptive power allocation and dynamic spectrum allocation across APs.
Design, Characterization and Modeling of Biobased Acoustic Foams
Keywords: Acoustic Absorption
Biobased polymers
Foam
Morphology design
Open cell
Porous structures

Polymeric open cell foams are widely used as sound absorbers in sectors such as automobile, aerospace, transportation and building industries, yet there is a need to improve sound absorption of these foams through understanding the relation between cell morphology and acoustic properties of porous material. Due to complicated microscopic structure of open cell foams, investigating the relation between foam morphology and acoustic properties is rather intricate and still an open problem in the field.The focus of this research is to design and develop biobased open cell foams for acoustic applications to replace conventional petrochemical based foams as well as investigating the link between cell morphology and macroscopic properties of open cell porous structures. To achieve these objectives, two industrially produced biomaterials, polylactide (PLA) and polyhydroxyalkanoate (PHA) and their composites were examined and highly porous biobased foams were fabricated by particulate leaching and compression molding. Acoustic absorption capability of these foams was enhanced utilizing the effect of co-continuous blends to form a bimodal porous structure. To tailor mechanical and acoustic properties of biobased foams, blends of PLA and PHA were studied to reach the desired mechanical and viscoelastic properties. To enhance acoustic properties of porous medium for having a broad band absorption effect, cell structure must be appropriately graded. Such porous structures with microstructural gradation are called Functionally Graded Materials (FGM). A novel graded foam structure was designed with superior sound absorption to demonstrate the effect of cell arrangement on performance of acoustic fixtures. Acoustic measurements were performed in a two microphone impedance tube and acoustic theory of Johnson-Champoux-Allard was applied to the fabricated foams to determine micro cellular properties such as tortuosity, viscous and thermal lengths from sound absorption impedance tube measurements using an inverse technique. As the next step towards in depth understanding of the relation between cell morphology and sound absorption of open cell foams, a semi-analytical model was developed to account for the effect of micro cellular properties such as cell wall thickness and reticulation rate on overall macroscopic and structural properties. Developed model provides the tools to optimize the porous structure and enhance sound absorption capability.
Considerations for a Targeted Self-management Program for Individuals with Traumatic Spinal Cord Injury
Keywords: qualitative
quantitative
self-management
spinal cord injury
traumatic

Evidence points to the need for increased self-management support efforts to reduce secondary complications in spinal cord injury (SCI). The overall objective of this thesis was to understand the phenomenon of self-management in individuals with traumatic SCI, and then based on this understanding; determine the implementation considerations for a targeted self-management program. This thesis used a mixed methods approach with an exploratory design. . Twenty-six interviews across three stakeholder groups were conducted in Phase I. In the first paper (qualitative), the following five facilitators to self-management were identified: physical support from the caregiver, emotional support from the caregiver, peer support and feedback, importance of positive outlook and acceptance, and maintaining independence. The following five barriers to self-management were identified: caregiver burnout, funding and funding policies, lack of accessibility, physical limitations and secondary complications, and difficulties achieving positive outlook or mood. In the second paper (qualitative), the meaning of self-management among the SCI and caregiver participants related principally to internal responsibility attribution. For the manager participants, the meaning was much narrower and the overarching theme of internal responsibility attribution that was observed among the SCI-caregiver dyads was not as widely expressed by this group. These findings informed the development of a survey that was administered nationally to individuals with traumatic SCI (n=99). In the third paper (quantitative), the components of a tailored self-management program were identified and included the preference for an internet-based program. The final paper examined the association between psychological characteristics in self-management and depression status in individuals with a traumatic SCI. Lower self-efficacy and mastery scores, as well as less time since injury, were associated with depression status. These findings could be used for the development, pilot-testing, and evaluation of a targeted self-management program for individuals with traumatic SCI.
The Application of Novel Positron Emission Tomography (PET) Radioligands as Imaging Biomarkers of Neurochemical Changes in the Brain: Relevance in Schizophrenia and Alzheimer's disease
Keywords: Alzheimer's disease
biomarkers
dopamine
neuroinflammation
PET imaging
Schizophrenia

The work of the thesis consists of five studies evaluating two Positron Emission Tomography (PET) radioligands and their molecular targets as imaging biomarkers of neurobiological abnormalities that occur in normal ageing and psychiatric illnesses. The first part of the thesis evaluated the use of [11C]-(+)-PHNO, which has affinity to dopamine D2/3 receptors, as an imaging biomarker of dopamine function. In the first study, [11C]-(+)-PHNO was used to evaluate the effect of personality differences on inter-individual variations of dopamine response to stress. In the second study, [11C]-(+)-PHNO was used to examine whether abnormalities in D2/3 receptor density could be present in the early phase of psychosis, specifically in individuals who have clinical high risk to develop psychosis and in antipsychotic- naïve patients with schizophrenia. The second part of the thesis evaluated the use of a novel second-generation Translocator protein 18kDa (TSPO) radioligand, [18F]-FEPPA, as an imaging biomarker of neuroinflammation. Although biomarker abnormalities may not be sufficient to produce an illness, the presence of biomarker abnormalities in non-affected healthy individuals may represent a biological vulnerability that may lead to an eventual development of a disease. In the third study of the thesis, I used [18F]-FEPPA to examine whether abnormalities in neuroinflammation can be detected in cognitively normal elderly individuals. The fourth study focused on a novel application of [18F]-FEPPA as an imaging biomarker of neuroinflammation in the white matter regions in healthy volunteers across normal adult life span. In this study, the caveats and limitations of [18F]-FEPPA quantification in the white matter regions were also explored. Finally, in the fifth study, [18F]-FEPPA was evaluated as an imaging biomarker of neuroinflammation in a clinical population by comparing the binding of [18F]-FEPPA in cognitively intact healthy control subjects and patients with Alzheimer's disease (AD) in both grey and white matter regions. The impact of neuroinflammation on cognitive function was evaluated by examining associations between several cognitive measures and [18F]-FEPPA binding in participants with AD. Collectively, these five studies demonstrate that PET radioligands can be used as imaging biomarkers to evaluate neurochemical changes that are present in both health and disease.