VictorJuiz/thesis huggingface dataset:
Characterizing the Organization within Alternative Lengthening of Telomere Associated-promyelocytic Leukemia Nuclear Bodies
Keywords: Alternative Lengthening of Telomeres
Promyelocytic Leukemia Nuclear Bodies
Electron Spectroscopic Imaging
Nuclear Organization

In the absence of telomerase activity, a subset of cancerous and immortalized cells maintain telomere length by means of a poorly understood mechanism, termed alternative lengthening of telomeres (ALT). Many details of telomere maintenance in ALT positive cells remain unclear, but significant evidence implicates a homologous recombination mechanism. ALT specific nuclear structures, known as ALT-associated promyelocytic leukemia nuclear bodies (APBs), are thought to serve as the site of telomere extension. Using electron spectroscopic imaging we have demonstrated that APBs contain substantial amounts of nucleic acid sequestered within the bodies. In contrast, promyelocytic leukemia nuclear bodies in non-ALT cell lines contain no significant nucleic acid. We show that the nucleic acid found in APBs is not RNA and provide evidence that it is in fact telomeric repeat DNA. This evidence supports a role for APBs to sequester extrachromosomal telomeric DNA in order to suppress the activation of DNA repair.
A Phage Display System to Profile the DNA-binding Specificities of C2H2 Zinc Fingers
Keywords: C2H2
zinc fingers
phage display
modular
DNA-binding specificity

Knowing the sequence specificities of transcription factors allows us to surmise their functions and establish their regulatory roles in genomes. The most common DNA-binding domain among eukaryotic transcription factors is the Cys2His2 zinc finger domain; however, despite their prevalence, the specificities of the majority of Cys2His2 zinc finger proteins remain unknown due to the difficulty in assaying them. My objective was to develop a new phage displayed-based assay, in which individual Cys2His2 domains are displayed on phage in an otherwise constant three-finger protein scaffold. In Chapter 2, I discuss evidence for the modularity of the Cys2His2 domain, since my assay requires that zinc fingers be modular. In Chapter 3, I describe my results on the development of this phage display-based assay. This work provides support for a new strategy to determine the specificities of individual zinc fingers, which can be used to infer specificities for multi-finger Cys2His2 proteins.
PKC Signaling Regulates Drug Resistance of Candida albicans and Saccharomyces cerevisiae via Divergent Circuitry Composed of the MAPK Cascade, Calcineurin and Hsp90
Keywords: Protein Kinase C
Drug Resistance
Candida albicans
Saccharomyces cerevisiae
Hsp90
Calcineurin

Treating fungal infections is challenging due to the emergence of drug resistance and the limited number of clinically useful antifungal drugs. To improve clinical outcome it will be necessary to develop new antifungal drugs with different mechanisms of action and to discover drugs that improve the fungicidal activity of current antifungals. This study reveals a new role for fungal protein kinase C (PKC) signaling in resistance to drugs targeting the ergosterol biosynthesis pathway in the pathogenic fungus, Candida albicans, and the model yeast, Saccharomyces cerevisiae. PKC signaling enabled survival of antifungal-induced cell membrane stress in part through the mitogen-activated protein kinase (MAPK) cascade and through cross-talk with calcineurin signaling in both species. The molecular chaperone Hsp90, which stabilizes client proteins including calcineurin, also stabilized the terminal C. albicans MAPK, Mkc1. This establishes new circuitry connecting PKC with Hsp90 and calcineurin, and suggests that inhibiting fungal Pkc1 can be a promising strategy for treating life-threatening fungal infections.
Polarization Model and Control in Fiber-based Bidirectional Systems with Reflections
Keywords: Fiber-optics
Polarization

We present, for the first time, methods to model and control the polarization of the output lightwave of a bidirectional fiber-optic system, in which the lightwave propagates through polarization control elements in both directions. Using the dynamic eigenstate (DES) principle, we built model to simulate the behavior of the polarization evolution. In a bidirectional system with one control element, we extracted system parameters from experimental data and achieved less than 3% angular deviation between modeled and experimental state of polarization (SOP). The theory was further validated by varying the input SOP to the bidirectional system. Our method can be extended to predict the SOP of a system with multiple actuators. Furthermore, combining our deterministic control method and a feedback loop, we are able to control the output SOP to be within a mean angular deviation of 5.5% from the target SOP, with as few as three iterations.
Patentability of Signals in Canada
Keywords: patentable subject matter
signal

This paper addresses the question of whether the patentability of signals is compatible with the law in Canada and attempts to develop a test for use in determining when a signal should be considered patentable subject matter. The hard-line position of the Canadian Intellectual Property Office, that signals are not patentable, is shown not to be supported in law. Canada’s domestic law is, in fact, compatible with the patentability of signals. Lessons are drawn from Europe, where signals are patentable and the United States, where they are not. Various international treaties are also examined for possible obligations concerning signals. Finally, an attempt is made to formulate a workable test for the patentability of signals that is compatible with Canadian legislation and case law.
Differential Effects of PPAR-γ Activation vs. Chemical or Genetic Reduction of DPP-4 Activity on Murine Bone Quality
Keywords: Bone Quality
Osteoporosis
Diabetes
Thiazolidinediones
DPP-4 Inhibitors

This study characterized the effects of two anti-diabetic drugs, a thiazolidinedione (TZD) and a Dipeptidyl Peptidase-4 (DPP-4) inhibitor on bone quality in a glucose intolerant mouse model. Bone quality in a DPP-4 -/- mouse model was also examined. Bone quality was evaluated through densitometry, mechanical testing and techniques to assess remodeling, structural and mineral properties. TZD treatment negatively affected trabecular mechanical properties in male, female and ovariectomized female (OVX) mice. Male mice exhibited the greatest effect due to TZD treatment with reduced vertebral vBMD, trabecular structure and bone formation. DPP-4 inhibitor treatment improved vertebral vBMD and trabecular architecture in female mice but improvements were lost in females following OVX. Male, female and OVX mice experienced increased trabecular mineralization due to DPP-4 inhibitor treatment. Genetic inactivation of DPP-4 did not produce a major bone phenotype in male and female mice but lead to reduced femoral geometry and mechanics in OVX mice.
Personality Foreshadows the Structure of Internalizing Disorders in Middle Childhood
Keywords: developmental psychopathology
internalizing
personality
structural models
middle childhood

The current investigation compared the fit of three models of internalizing in middle childhood: (1) a unitary factor model, (2) a two-factor model corresponding to the DSM-IV Anxiety/Depression distinction, and (3) a two-factor model corresponding to the Fear/Distress distinction observed in structural studies of adult psychopathology (Krueger, 1999; Slade & Watson, 2006). Mothers of 344 children (50.6% female, mean age = 9.97, SD = .82) reported on childhood internalizing symptoms and personality traits. Confirmatory factor analyses revealed acceptable fit indices for all three models. The unitary factor model provided the most parsimonious fit to the data. Although the structural analyses suggested that internalizing subfactors were not differentiated in middle childhood, hierarchical regression analyses revealed that personality dimensions uniquely predicted fear and distress disorders. These results suggest that personality foreshadows later psychopathology structure before it is manifest at the symptom level.
Dynamic Categorization: What We Can Learn from the Emergent Arrangement of Physical Artifacts in Libraries
Keywords: Libraries
categorization
RFID
Radio Frequency Identification
browsing
folksonomies
retrieval
emergent

Radio frequency identification (RFID) is a technology used in many applications for the identification of objects. This thesis presents a concept of how libraries could use RFID technology to locate physical items within the library. The ability to locate items within the library changes the way users interact with physical material, creates new ways of user collaboration, and influences the ability to browse the shelves for physical items. Several implementation scenarios are presented in detail and implications on collaboration and browsing are analyzed.
The Functional Integration of Adult-born Granule Cells into Dentate Gyrus Circuitry
Keywords: neurogenesis
dentate gyrus

New neurons are generated throughout adulthood in the dentate gyrus of the hippocampus. The aim of the current study was to address whether differences in the morphological complexity of adult-born granule cells affect their integration into existing dentate gyrus circuitry. To selectively label proliferating cells, we injected a CAG-retrovirus into the dentate gyrus of mice. Either 10, 20, 40, or 80 days following viral infection, mice were injected with pentylenetetrazol (PTZ) to induce hippocampal activation, and expression of the immediate early gene c-fos was used as a marker of activated neurons. We then compared morphological features of neurons across age groups and between Fos+ and Fos- neurons within each age group. We found that dendritic length and branch number increased from 10 to 20 days post infection. Unexpectedly, we also found that dendritic length and branch number decreased from 20 to 40 days post infection, suggesting that the maturation of adult-generated neurons is associated with an active pruning process. Furthermore, we found no significant difference in morphological complexity between Fos+ and Fos- neurons, suggesting that dendritic morphology does not influence integration into dentate gyrus circuitry.
Forfeited: Civil Forfeiture and the Canadian Constitution
Keywords: Constitutional Law
Criminal Law
Forfeiture
Charter
Constitution Act, 1867
Division of Powers
Paramountcy
Property

The enactment of civil asset forfeiture legislation by Alberta and Ontario in the fall of 2001, followed by the passage of similar legislation in five other provinces, has signalled a dramatic change in the way Canadian constitutional law ought to be understood. This thesis builds on American legal scholarship by highlighting how deficiencies in Canada’s constitutional law could create space for more invasive civil forfeiture statutes. Following a historical overview of forfeiture law in Canada, the thesis (i) examines how the Supreme Court of Canada mischaracterized this legislation as a matter of property and civil rights; (ii) considers whether the doctrine of federal paramountcy should have rendered the legislation inoperable and the consequences of the failure by the Court to do so; and (iii) evaluates iiithe impact of the absence of an entrenched property right in the constitution, in regard to this matter.
Time-dependent Photomodulation of a Single Atom Tungsten Tip Tunnelling Barrier
Keywords: Photoemission
Tungsten
general solution to partial differential equations
Schrodinger equation
Field emission
Fowler-Nordheim
photomodulation
solving complex band structure

There has been much work on electron emission. It has lead to the concept of the photon and new electron sources for imaging such as electron microscopes and the rst formulation of holographic reconstructions [1-6]. Analytical derivations are important to gain physical insight into the problem of developing better electron sources. However, to date, such formulations have su ered by a number of approximations that have masked important physics. In this thesis, a new approach is provided that solves the Schrodinger wave equation for photoemission from a single atom tungsten tip barrier or more generally, for photoemission from a Schottky triangular barrier potential, with or without image potential e ects. We describe the system, then introduce the mathematical derivation. We conclude with the applications of the theory.
Syntaxin-3 Regulates Biphasic Glucose Stimulated Insulin Secretion in the Pancreatic Beta Cell
Keywords: Insulin Secretion
Syntaxin
SNAREs
Exocytosis

Our study aims to investigate the role of Syntaxin-3 in glucose stimulated insulin secretion (GSIS) and how it regulates the recruitment to plasma membrane and/or exocytotic fusion of insulin granules. We examined endogenous Syn-3 function by down-regulating its expression using siRNA/lenti-shRNA, which impaired GSIS. Although Syn-3 depleted cells showed no change in the number and fusion of docked granules, there was a reduction in newcomer granules and their subsequent exocytotic fusion. We then examined the effects of overexpressing Syn-3-WT, which enhanced biphasic GSIS. Since open conformation (OF) Syn-1A was reported to enhance exocytosis by promoting SNARE complex formation, we constructed OF Syn-3. Exogenous OF Syn-3 had no effect on secretion as it is unable to be trafficked to insulin granules. Taken together, we conclude that Syn-3 facilitates mobilization of newcomer insulin granules to the plasma membrane, to contribute to both first and second phase of GSIS in pancreatic beta cells.
Interaction Between the Effects of Preparation Method and Variety on the Glycemic Index of Novel Potato Varieties
Keywords: Glycemic Index
Potatoes
In-vivo Digestability
Starch

As part of a project to see whether potatoes with a low glycemic-index (GI) could be developed through plant breeding, the GI values of 4 new potato varieties differing in starch structure was determined in 3 studies over 2 years in human subjects. Since cooking and cooling affects starch structure the potatoes were studied both freshly cooked (boiled) and cooled. The first study showed that cooling reduced the GI of two varieties by 40-50% but had no effect in the others (treatment × variety interaction, p=0.024), an effect which was confirmed in study 2. Differences in GI were readily explained by differences in starch structure or in-vitro digestion rate. Carbohydrate malabsorption increased from 3 to 5% upon cooling, not enough to account for the reduced GI. It is concluded that the effect on GI of cooling cooked potatoes varies in different varieties. Further research is needed to understand the mechanism.
Investigating the Process of Cement Line Maturation on Substrate Surfaces with Submicron Undercuts
Keywords: Cement Line
Bone Implant Interface
Submicron Undercuts
Bone-bonding

The cement line is the first mineralized matrix deposited on an implant surface during contact osteogenesis forming the bone/implant interface. The hypothesis underlying the present project was that non-collagenous cement line proteins must be deposited into the submicron undercuts on substrate surfaces prior mineralization. In vitro osteogenic cultures were used to grow bone nodules on Thermanox® coverslips modified with calcium phosphate nanocrystals, creating an undercutted surface. Electron microscopy was used to observe cement line formation. BSP immunogold labelling was used to determine if the cement line organic matrix is deposited within undercuts prior mineralization. The results showed the deposited bone nodules, and on test coverslips the deposited cement line was thicker and evenly distributed than control. Furthermore, positive BSP labelling was found within the undercuts prior to cement line mineralization. Thus, it can be concluded that cement line proteins are deposited into submicron undercuts on substrate surfaces prior to mineralization.
Investigating the Roles of Homeobox Containing Transcription Factors Iroquois 3/5 in Mammalian Heart Development and Electrophysiology
Keywords: Iroquois
homeobox
heart development
cardiac electrophysiology
cardiac transcription factor

Iroquois homeobox (Irx) family members, a group of highly conserved homeodomain containing transcription factors, are involved in the patterning and the proper functions of vertebrate organs. They can act as transcriptional activators or repressors in a context-dependent manner. Preliminary data indicated that Irx3 and Irx5 are functionally redundant during cardiac morphogenesis, and they physically interact with other cardiac transcription factors. At E14.5, outflow tract septation failure and ventricular septation failure were observed in Irx3/5DKO mouse hearts. Loss of Irx3/5 in neural crest and endothelial cell lineages led to outflow tract septation failure and ventricular septal defect. In adult mice, Irx3 is expressed in the atrioventricular conduction system, and loss of Irx3 leads to slower ventricular conduction velocity. qRT-PCR analysis and immunofluorescence staining revealed that the expression of gap junction proteins, Cx40 and Cx43, are affected by the loss of Irx3. Over-expression of Irx3 and a dominant repressor form of Irx3, Irx3-EnR, resulted in Cx40 upregulation, indicating that Irx3 acts as an indirect positive regulator of Cx40. Irx3-EnR over-expression in vivo resulted in postnatal onset of atrial enlargement, ventricular hypertrophy, and conduction failure. Taken together, this study demonstrates the significance of Irx3/5 in both cardiovascular development and cardiac electrophysiology.
Precoding and Resource Allocation for Multi-user Multi-antenna Broadband Wireless Systems
Keywords: Resource Allocation
Precoding
MIMO-OFDMA
Stream Rate Allocation
Time-Reversal Space-Time Block Coding
Tomlinson-Harashima precoding
Weighted Sum-Rate MAximization
Weighted MMSE Minimization

This thesis is targeted at precoding methods and resource allocation for the downlink of fixed multi-user multi-antenna broadband wireless systems. We explore different utilizations of precoders in transmission over frequency-selective channels. We first consider the weighted sum-rate (WSR) maximization problem for multi-carrier systems using linear precoding and propose a low complexity algorithm which exhibits near-optimal performance. Moreover, we offer a novel rate allocation method that utilizes the signalto- noise-ratio (SNR) gap to capacity concept to choose the rates to allocate to each data stream. We then study a single-carrier transmission scheme that overcomes known impairments associated with multi-carrier systems. The proposed scheme utilizes timereversal space-time block coding (TR-STBC) to orthogonalize the downlink receivers and performs the required pre-equalization using Tomlinson-Harashima precoding (THP).We finally discuss the strengths and weaknesses of the proposed method.
The Hormonal Regulation of Kisspeptin and Neuropeptide Y Hypothalamic Neurons
Keywords: kisspeptin
neuropeptide Y
estrogen
hypothalamus
immortalized cell lines

Kisspeptin (encoded by Kiss1) is a hypothalamic neuropeptide that is directly regulated by sex steroids and directly stimulates gonadotropin-releasing hormone (GnRH) neurons. Kisspeptin cell models were established in order to facilitate future molecular analysis of kisspeptin. mHypoA-51 and mHypoA-63 cell lines were found to express kisspeptin, estrogen receptor α and β, substance P, but not tyrosine hydroxyase. Furthermore, estrogen decreased Kiss1 expression in both cell lines. Based on these results, it was concluded that mHypoA-51 and mHypoA-63 are representative of arcuate kisspeptin neurons. Accumulating evidence also indicates that kisspeptin indirectly stimulates GnRH neurons through afferent neurons. Kisspeptin receptor expression was detected in native neuropeptide Y (NPY) neurons. Using the mHypoE-38 cell line, kisspeptin was found to directly regulate NPY mRNA expression and secretion via the ERK1/2 and p38 MAPK pathways. This is the first evidence that kisspeptin directly stimulates NPY neurons to potentially exert indirect effects on GnRH neurons.
Global Position Effects on the Epigenetics of Variegated Lentiviral Vector Expression in Embryonic Stem Cells
Keywords: Epigenetics
Retrovirus
Embryonic Stem Cells
Variegation
Viral Expression
Chromatin Structure
Lentivirus
Integration Site
Gene Therapy
Bioinformatics

Lentivirus efficiently transduce stem cells, however are notably silenced in embryonic stem cells (ESC). Provirus can be silent, expressing, or variegated when clonal single copy ESCs spawn daughters that revert expression despite containing identical integration sites (IS) indicating epigenetic regulation. In the silent state, variegated provirus are bound by H1 and MeCP2, where H1 compensates for MeCP2 binding in DNA methylation null ESCs, consistent with a model of heterochromatin formation dependent on concentrations of its constituent components. ESC Variegation was hypothesized to result from spreading of nearby heterochromatin. Global IS analysis indicates Variegated IS favour gene deserts, repeat clusters, and LINEs while Expressers prefer gene density with stable modest expression and SINEs. Chromatin data does not support a role for the spread of heterochromatin possibly a consequence of the dynamic/dispersed nature of ESC heterochromatin. Variegation thus may depend on stochastic chromatin regulation by pluripotency factors at proximal genome organizing repeats.
Effects of Biodiesel Fuelling on Diesel Particulate Matter
Keywords: Biodiesel
Biofuels
Particulate Matter
Diesel
Diesel Particulate Filter
Microstructure
Regeneration

Diesel particulate matter (PM) produced from Ultra Low Sulfur Diesel (ULSD), Soy-derived B20 and Animal fat-derived B20 was collected at two engine operating conditions. Gravimetric analysis showed the PM emissions to depend on both fuel and engine operating condition. B20 fuels exhibited higher PM emissions at low load conditions, but lower PM emissions under high load conditions. The differences between the operating conditions were less significant for B20 fuels than for ULSD. Elemental Carbon analysis revealed the B20 PM to contain greater proportions of organic carbon, which may improve diesel particulate filter (DPF) regeneration. Finally, TEM images showed considerable differences between ULSD and B20 soot at low engine loads. The B20 soot displayed a more disordered arrangement of graphene layers. At higher loads, the differences are subtle, but the B20 PM still displayed a more amorphous structure. There was little difference between the Soy and Animal fat-derived B20 soot.
The Transformation of Landscapes in Southwest Montréal and Identity Formation During the Quiet Revolution
Keywords: historical geography
Montréal
Québec Studies
Canadian Studies
urban planning

In this thesis I demonstrate how the social and physical construction of spaces in Montréal‘s CBD during the Quiet Revolution marginalized working-class, inner-city manufacturing districts. To address this research question, I work across a variety of secondary sources and employ census data and reports to analyze demographic changes as well as other indices that illustrate the impact of local economic restructuring. In order to understand identity formation that is related to yet distinct from the mechanisms of capital, I examine archival documents that trace the urban growth regime’s nationalist-inflected vision of high-modernity that was inscribed onto the city’s landscape. I focus on the appropriation of landscapes in working-class Southwest Montréal. I situate these landscape transformations in a longer history of class formation in which a colonized Francophone bourgeoisie attempted to reverse its socioeconomic circumstances that were partly a consequence of the British conquest.