VictorJuiz/thesis huggingface dataset:
Genetic Determinants of Carbohydrate Consumption
Keywords: Nutrigenomics
Carbohydrate
Sugars
Genetics
Polymorphism

Background: There are a number of biological pathways that affect our ingestive behaviours, including energy homeostasis, food reward, and taste. Given that carbohydrates such as sugars, provide energy and a sweet taste, examining candidate genes in each pathway may help explain differences in carbohydrate consumption behaviours. Objective: To determine whether variations in genes encoding a glucose transporter (GLUT2), a dopamine receptor (DRD2), and sweet taste receptor (TAS1R2) are associated with differences in sugar consumption in two distinct populations. Methods: Population 1 included diabetes-free young adults where dietary intake was assessed using a one month 196-item food frequency questionnaire (FFQ). Population 2 consisted of individuals with type 2 diabetes. Dietary intake was assessed using 3-day food records administered 2 weeks apart; food record 1 (FR1) and 2 (FR2). Subjects were genotyped for the Thr110Ile variation in GLUT2 (n1=587; n2=100), the C957T variation in DRD2 (n1=313; n2=100), and the Ser9Cys and Ile191Val variations in TAS1R2 (n1=1037; n2=100) using real-time PCR. Results: In comparison to individuals homozygous for the GLUT2 Thr allele, consumption of sugars was higher among Ile carriers in population 1 (133 ± 5 vs 118 ± 3 g/d, p=0.006) and population 2 on two separate food records (FR1: 112 ± 9 vs 87 ± 5 g/d, p=0.02; FR2: 105 ± 8 vs 78 ± 4 g/d, p=0.002). For the C957T variation in population 1, we detected a significant DRD2xSex interaction with the consumption of sucrose decreasing with each T allele among men (p=0.03) and a heterosis mode of inheritance among women where heterozygotes consumed the most (p=0.01). For TAS1R2, we detected a significant TAS1R2xBMI interaction and among overweight individuals, carriers of the Val allele consumed less sugars than those with the Ile/Ile genotype (103 ± 6 vs122 ± 6 g/d, p=0.01). In population 2, carriers of the Val allele consumed less sugars than individuals with the Ile/Ile genotype (83 ± 6 vs 99 ± 6 g/d, p=0.04) on FR2. Conclusions: Our findings demonstrate that genetic variation in GLUT2, DRD2 and TAS1R2 affect habitual sugar consumption and suggest that selection of dietary sugars can be influenced by different biological pathways.
Theory and Applications of Multiconductor Transmission Line Analysis for Shielded Sievenpiper and Related Structures
Keywords: Multiconductor transmission lines
Wave propagation in periodic structures

This thesis focuses on the analytical modeling of periodic structures which contain bands with multiple modes of propagation. The work is motivated by several structures which exhibit dual-mode propagation bands. Initially, transmission line models are focused on. Transmission line models of periodic structures have been used extensively in a wide variety of applications due to their simplicity and the ease with which one can physically interpret the resulting wave propagation effects. These models, however, are fundamentally limited, as they are only capable of capturing a single mode of propagation. In this work multiconductor transmission line theory, which is the multi-mode generalization of transmission line theory, is shown to be an effective and accurate technique for the analytical modeling of periodically loaded structures which support multiple modes of propagation. Many results from standard periodic transmission line analysis are extended and generalized in the multiconductor line analysis, providing a familiar intuitive model of the propagation phenomena. The shielded Sievenpiper structure, a periodic multilayered geometry, is analyzed in depth, and provides a canonical example of the developed analytical method. The shielded Sievenpiper structure exhibits several interesting properties which the multiconductor transmission line analysis accurately captures. It is shown that under a continuous change of geometrical parameters, the dispersion curves for the shielded structure are transformed from dual-mode to single-mode. The structure supports a stop-band characterized by complex modes, which appear as pairs of frequency varying complex conjugate propagation constants. These modes are shown to arise even though the structure is modeled as lossless. In addition to the periodic analysis, the scattering properties of finite cascades of such structures are analyzed and related to the dispersion curves generated from the periodic analysis. Excellent correspondence with full wave finite element method simulations is demonstrated. In conclusion, a physical application is presented: a compact unidirectional ring-slot antenna utilizing the shielded Sievenpiper structure is constructed and tested.
Soil Microbial and Nutrient Dynamics During Late Winter and Early Spring in Low Arctic Sedge Meadows
Keywords: microbial ecology
soil biogeochemistry
Arctic ecology
nutrient cycling

Microbial activity occurs year-round in Arctic soils, including during the winter when soils are frozen. From 2004 to 2008 I monitored soil microbial and nutrient dynamics in low Arctic wet and dry sedge meadows near Churchill, Manitoba. I documented a consistent annual pattern in which soil microbial biomass (MB) and soil nutrients peak in late winter, and decrease during the early stages of spring thaw, remaining in low abundance during the summer. Based on a series of experiments, resource shortages do not appear to be the cause of the microbial decline, as has been hypothesized. Observations and theoretical considerations regarding soil physical properties indicate that this decrease is driven by the influx of liquid water at thaw that brings about a rapid change in the chemical potential of water, leading to cell lysis. I have used 15N isotope tracing to show that inorganic nitrogen is taken up very quickly at thaw by the roots of the dominant plant, Carex aquatilis. This represents a critical window of opportunity for these plants, as nitrogen remains abundant only for a short time. The described annual pattern was pronounced in wet sedge sites, but some inter-annual variation is evident, for example a post-thaw soil nitrogen pulse in 2006, and low winter MB in 2008. In the dry sedge meadow, fluctuations in MB and nutrients were dampened relative to wet sites, and the annual pattern was variable, particularly after 2006. Over four years, peak winter values of soil MB and nutrient variables declined in both wet and dry sites, and this could be related to a drying trend. This work improves our understanding of the controls on decomposition and primary productivity in a system that is experiencing climate warming and increased precipitation. Changes to hydrology, carbon and nitrogen cycling, and primary productivity will have further effects on vegetation communities and higher trophic levels, including several species of migratory birds.
Linear, Discrete, and Quadratic Constraints in Single-image 3D Reconstruction
Keywords: computer vision
3D reconstruction
shape from texture
shape from planar curves
shape from shading
single view modeling
structured light
GBR ambiguity
shading ambiguity

In this thesis, we investigate the formulation, optimization and ambiguities in single-image 3D surface reconstruction from geometric and photometric constraints. We examine linear, discrete and quadratic constraints for shape from planar curves, shape from texture, and shape from shading. The problem of recovering 3D shape from the projection of planar curves on a surface is strongly motivated by perception studies. Applications include single-view modeling and uncalibrated structured light. When the curves intersect, the problem leads to a linear system for which a direct least-squares method is sensitive to noise. We derive a more stable solution and show examples where the same method produces plausible surfaces from the projection of parallel (non-intersecting) planar cross sections. The problem of reconstructing a smooth surface under constraints that have discrete ambiguities arise in areas such as shape from texture, shape from shading, photometric stereo and shape from defocus. While the problem is computationally hard, heuristics based on semidefinite programming may reveal the shape of the surface. Finally, we examine the shape from shading problem without boundary conditions as a polynomial system. This formulation allows, in generic cases, a complete solution for ideal polyhedral objects. For the general case we propose a semidefinite programming relaxation procedure, and an exact line search iterative procedure with a new smoothness term that favors folds at edges. We use this numerical technique to inspect shading ambiguities.
The Hormonal Contol of Neuropeptide Y and Gonadotropin-releasing Hormone Hypothalamic Neurons
Keywords: Hypothalamus
leptin estrogen

The physiological mechanisms that control energy homeostasis are reciprocally linked to reproduction. However, the neuroendocrine circuitry that registers endocrine cues to direct homeostatic responses in energy balance and reproduction remain unknown. Neuropeptide Y (NPY) neurons have emerged as a key central target of estrogen and leptin that are capable of modulating both reproduction and energy balance. The hypothesis was generated that NPY neuronal subpopulations act as an integration centre to regulate the effects of estrogen and leptin on these important physiological processes through specific signaling pathways. Using hypothalamic cell lines that express the leptin receptor (Ob-R), estrogen receptor (ER) and NPY, this hypothesis was tested in three aims. 17β-estradiol (E2) was previously demonstrated to biphasically regulate NPY mRNA in the mHypoE-38 neuronal cell line; where 24 h E2 exposure induced NPY gene expression that our group proposed may be involved in the gonadotropin-releasing hormone (GnRH) preovulatory surge. E2 also acts as an anorexigenic hormone through unknown hypothalamic targets. E2 directly decreased NPY secretion in the mHypoE-42 and mHypoA-2/12 neuronal cell lines through ER-α. The anorexigenic action of E2 was mediated through the energy sensing 5’ AMP-activated protein kinase (AMPK) and the phosphoinositide-3-kinase (PI3K) pathway. NPY secretion was also decreased by leptin in mHypoA-59 and NPY-GFP cell models through AMPK- and PI3K-dependent mechanisms. Prolonged exposure to leptin in NPY-GFP cell lines prevented AMPK signaling and the leptin-mediated reduction in NPY secretion, indicating NPY neuronal resistance with prolonged leptin exposure. Leptin also stimulated NPY secretion in mHypoE-38 neurons, which was blocked by pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) and PI3K pathways. Importantly, conditioned medium from the mHypoE-38 NPY neuronal cells induced GnRH transcripts in GT1-7 neurons, which was inhibited by Y1-receptor antagonists. Pharmacological inhibitors of the MAPK and PKA signal transduction pathways attenuated the NPY-mediated increase in GnRH transcription. Based upon these findings, I propose NPY neurons in the hypothalamus consist of a heterogeneous population of neurons, and provide the first evidence of intrinsically different responses to function as physiological integrators for two different systems: NPY secretion can be suppressed to decrease food intake and induced to stimulate GnRH neurons.
Characterization of the Role of Elg1-RFC in Suppression of Genome Instability
Keywords: Biochemistry
Molecular Biology

Sliding clamps and their cognate clamp loaders facilitate DNA synthesis, DNA repair, and sister chromatid cohesion in eukaryotes. ELG1 (enhanced level of genome instability) encodes a member of the fourth clamp-loader-like complex identified to date, and is important in the maintenance of genome integrity. Like all clamp loaders, Elg1 is a replication factor C (RFC) homologue. I examined the roles of the unique and conserved regions of S.cerevisiae Elg1 in resistance to exogenous DNA damage and suppression of spontaneous DNA damage. The conserved RFC region of Elg1 mediates association with chromatin function. The unique C- terminus of Elg1 mediates oligomerization with Rfc2-5, a core complex present in all clamp loaders, and is essential for Elg1 function. Finally, the N-terminus of Elg1 promotes its nuclear localization and contributes to the maintenance of genome stability. The Elg1-RFC complex most likely functions in collaboration with the sliding clamp PCNA. Combining mutations in ELG1 and PCNA results in endogenous DNA damage, which activates a noncanonical DNA damage response that results in upregulation of dNTP production. Increased dNTP pools allow significant DNA synthesis to occur at hydroxyurea (HU) concentrations that prevent replication in wild type cells. However, consistent with the recognized correlation between dNTP levels and spontaneous mutation, the double mutant exhibits a significant increase in mutation frequency. These phenotypes are also detectable in the single mutants although to a lesser extent. Together, these findings suggest that spontaneous mutagenesis stimulated by endogenous DNA damage may be a general feature of the DNA damage response.
Dynamic Tensile, Flexural and Fracture Tests of Anisotropic Barre Granite
Keywords: Experiment
Dynamic
Rock
SHPB
Anisotropy
Tensile Strength
Fracture Toughness

Granitic rocks usually exhibit strongly anisotropy due to pre-existing microcracks induced by long-term geological loadings. The understanding of anisotropy in mechanical properties of rocks is critical to a variety of rock engineering applications. In this thesis, the anisotropy of tension-related failure parameters involving tensile strength, flexural strength and Mode-I fracture toughness/fracture energy of Barre granite is investigated under a wide range of loading rates. Three sets of dynamic experimental methodologies have been developed using the modified split Hopkinson pressure bar system; Brazilian test to determine the tensile strength; semi-circular bend method to determine the flexural strength; and notched semi-circular bend method to determine the Mode-I fracture toughness and fracture energy. For all three tests, a simple quasi-static data analysis is employed to deduce the mechanical properties; the methodology is assessed critically against the isotropic Laurentian granite. It is shown that if dynamic force balance is achieved in SHPB, it is reasonable to use quasi-static formulas. The dynamic force balance is obtained by the pulse shaper technique. To study the anisotropy of these properties, rock blocks are cored and labeled using the three principal directions of Barre granite to form six sample groups. For samples in the same orientation group, the measured strengths/toughness shows clear loading rate dependence. More importantly, a loading rate dependence of the strengths/toughness anisotropy of Barre granite has been first observed: the anisotropy diminishes with the increase of loading rate. The reason for the strengths/toughness anisotropy can be understood with reference to the preferentially oriented microcracks sets; and the rate dependence of this anisotropy is qualitatively explained with the microcracks interaction. Two models abstracted from microscopic photographs are constructed to interpret the rate dependence of the fracture toughness anisotropy in terms of the crack/microcracks interaction. The experimentally observed rate dependence of the anisotropy is successfully reproduced.
Exploiting Linguistic Knowledge to Infer Properties of Neologisms
Keywords: Computer science
Computational linguistics
Natural language processing
Lexical acquisition
Neologisms

Neologisms, or newly-coined words, pose problems for natural language processing (NLP) systems. Due to the recency of their coinage, neologisms are typically not listed in computational lexicons---dictionary-like resources that many NLP applications depend on. Therefore when a neologism is encountered in a text being processed, the performance of an NLP system will likely suffer due to the missing word-level information. Identifying and documenting the usage of neologisms is also a challenge in lexicography, the making of dictionaries. The traditional approach to these tasks has been to manually read a lot of text. However, due to the vast quantities of text being produced nowadays, particularly in electronic media such as blogs, it is no longer possible to manually analyze it all in search of neologisms. Methods for automatically identifying and inferring syntactic and semantic properties of neologisms would therefore address problems encountered in both natural language processing and lexicography. Because neologisms are typically infrequent due to their recent addition to the language, approaches to automatically learning word-level information relying on statistical distributional information are in many cases inappropriate. Moreover, neologisms occur in many domains and genres, and therefore approaches relying on domain-specific resources are also inappropriate. The hypothesis of this thesis is that knowledge about etymology---including word formation processes and types of semantic change---can be exploited for the acquisition of aspects of the syntax and semantics of neologisms. Evidence supporting this hypothesis is found in three case studies: lexical blends (e.g., "webisode" a blend of "web" and "episode"), text messaging forms (e.g., "any1" for "anyone"), and ameliorations and pejorations (e.g., the use of "sick" to mean `excellent', an amelioration). Moreover, this thesis presents the first computational work on lexical blends and ameliorations and pejorations, and the first unsupervised approach to text message normalization.
Characterizing the Role of Regulator of G-protein Signalling 4 as a Mediator of Sinoatrial Node and Atrial Cardiomyocyte Function
Keywords: RGS4
atrial fibrillation
parasympathetic

Heart rate is modulated by the opposing activities of sympathetic and parasympathetic inputs to pacemaker cardiomyocytes in the sinoatrial (SA) node. Parasympathetic activity on nodal myocytes is mediated by acetylcholine-dependent stimulation of M2 muscarinic receptors and activation of Gαi/o signalling. Although, regulators of G-protein signalling (RGS) proteins are potent inhibitors of Gαi/o signalling in many tissues, the RGS protein(s) that regulate parasympathetic tone in the SA node are unknown. Our results demonstrate that RGS4 mRNA levels are higher in the SA node compared to right atrium. Conscious freely moving RGS4-null mice showed a greater extent of bradycardia in response to parasympathetic agonists compared to wild-type animals. Moreover, anaesthetized rgs4-null mice had lower baseline heart rates and greater heart rate increases following atropine administration. Retrograde-perfused hearts from rgs4-null mice also showed enhanced negative chronotropic responses to carbachol, while isolated SA node myocytes showed greater sensitivity to carbachol-mediated reduction in the action potential firing rate. Finally, rgs4-null SA node cells showed decreased levels of G-protein-coupled inward rectifying potassium (GIRK) channel desensitization, and altered modulation of acetylcholine-sensitive potassium current (IKACh) kinetics following carbachol stimulation. Taken together, our studies establish that RGS4 plays an important role in regulating sinus rhythm by inhibiting parasympathetic signalling and IKACh activity. Following these results, we predicted that loss of RGS4 expression and function will result in increased levels of parasympathetic effector activity leading to increased susceptibility to atrial fibrillation. Susceptibility to atrial fibrillation (AF) depends strongly on parasympathetic activity. Since RGS4 inhibits parasympathetic / M2-dependent Gαi/o signalling in the SA node, we explored whether changes in RGS4 levels altered the susceptibility of atrial fibrillation. We found that, RGS4 levels were decreased in atria of tachypaced dogs prior to their development of chronic AF. Moreover, in vivo ECG recordings of anaesthetized mice showed greater susceptibility to AF while optical mapping of isolated atrial preparations using a voltage-sensitive dye revealed greatly increased susceptibility to rotor formation when RGS4 was ablated. Consistent with altered parasympathetic signalling in the myocardium of rgs4-null mice, IKACh evoked by carbachol application were greater in isolated atrial myocytes from rgs4-null mice. These IKACh changes were, as expected, associated with marked action potential duration shortening in response to parasympathetic activation, but not to slower conduction velocities. Together, our findings establish that RGS4 protects atrial tissues from excess parasympathetic signalling that predispose to atrial fibrillation.
Functional Dissection of Lupus Susceptibility Loci on the New Zealand Black Mouse Chromosome 1
Keywords: Systemic Lupus Erythematosus
Mouse Model

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong and complex genetic basis. To dissect the function of the lupus susceptibility loci on New Zealand black (NZB) mouse chromosome 1, the lab had previously generated congenic mice with an introgressed homozygous NZB chromosome 1 intervals extending from ~35 or ~82 to 106 cM on the C57BL/6 background. Although both mouse strains made IgG anti-nuclear antibodies (ANAs), ANA titres and cellular activation were significantly higher in mice with the longer interval. These studies suggest the presence of two susceptibility genes. In this thesis I have sought to further characterize the cellular abnormalities and underlying genetic polymorphisms that produce them in these mice. Using mixed hematopoietic chimeric mice, with a mixture of tagged-B6 and congenic bone marrow I demonstrate that there are intrinsic B and T cell functional defects in chromosome 1 congenic mice. I further show that an intrinsic B cell defect is required for efficient recruitment of B cells into the spontaneous germinal centres and differentiation of autoantibody producing cells in these mice. To more precisely localize the susceptibility loci, I produced and characterized a number of additional subcongenic mouse strains. This revealed surprising genetic complexity with the presence of at least four lupus susceptibility loci and a suppressor locus on chromosome 1, several of which appeared to impact on T cell function. Finally, I generated bicongenic mice carrying both NZB chromosome 1 and 13 intervals, hypothesizing that since these were two of the major intervals associated with autoimmune disease in NZB mice they would fully recapitulate the autoimmune phenotypes. Although this hypothesis was incorrect, several novel phenotypes developed including marked expansion of the plasmacytoid and myeloid dendritic cell compartments and increased BAFF and IgA autoantibody production. Although this expansion was associated with TLR hyper-responsiveness, disease severity remained mild, possibly due to the lack of IFN- production, which appeared to be inhibited in these mice. Thus, lupus arises from immune defects affecting several cellular populations, which are the product of multiple genetic polymorphisms that interact in a complex fashion to produce the autoimmune phenotype.