VictorJuiz/thesis huggingface dataset:
Peripherin-28 as a Biomarker of ALS: A Methodological Study
Keywords: Peripherin
Neurofilament Light
TDP-34
ELISA
amyotrophic lateral sclerosis
Per28
TDP-43 C-Splice
NFL-60
cerebrospinal fluid
biomarkers
alternative splicing

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease which currently lacks rapid and definitive diagnostic tests. Recently identified neuron specific splice variant molecules, Per28 and NFL-60, have been shown to contain unique epitopes and to have altered levels of expression in ALS patients. It is believed that these factors make Per28 and NFL-60 excellent candidate biomarkers for the ALS disease state. In this study, we attempted to develop ELISA assays directed against Per28 and NFL-60, as well as a generalized guideline for splice variant ELISA development, which could be used in a clinical setting. Limitations in currently identified antibodies to the splice variants allowed only for the completion of a Per28 ELISA, which lacked the sensitivity for clinical relevance. This assay creation process, however, did produce a guideline for similar ELISA development, which should allow for the more expeditious creation future ELISA.
Myocyte Androgen Receptor Modulates Body Composition and Metabolic Parameters
Keywords: endocrinology
metabolism
androgens
skeletal muscle
adipose tissue
transgenic
androgen receptor
testosterone

Androgens (such as testosterone) have been shown to increase lean body mass and reduce fat body mass in men through activation of androgen receptors (AR). While this suggests a potential clinical use for androgens, attempts at utilization of this class of hormones as a therapeutic are limited by side effects due to indiscriminate AR activation in various tissues. Thus, a greater understanding of the tissues and cells involved in promoting these changes would be beneficial. Here we show that selective overexpression of AR in muscle cells of transgenic (HSA-AR) rodents both increases lean muscle mass and significantly reduces fat mass in males. Similar effects can be induced in HSA-AR females treated with testosterone. Metabolic analyses of HSA-AR males show that these animals demonstrate increased O2 consumption and hypermetabolism. Thus, targeted activation of AR in muscle regulates body composition and metabolism, suggesting a novel target for drug development.
Attempts to Elucidate the Role of SNAP23 in Regulated and Pathological Exocytosis in Pancreatic Acinar Cells Using an Inducible SNAP23 Knockout Mouse
Keywords: pancreatic acinar cell
exocytosis
SNAP23
pHluorin

One contentious issue regarding pancreatic acinar exocytosis concerns which SNAP25 isoform (SNAP23/29/47) mediates the various fusion events in this cell type. Based on dominant-negative over-expression studies, SNAP23 was hypothesized to be the putative isoform mediating apical exocytosis, basolateral exocytosis, and ZG-ZG fusion. Unfortunately, using a SNAP23 KD mouse model, 80% SNAP23 KD was insufficient to manifest any secretion phenotype. A novel syncollin-pHluorin exocytosis imaging technique initially meant to assess which fusion events are perturbed by SNAP23 KD was successfully developed and displayed improvements over previous imaging techniques. The syncollin-pHluorin imaging enabled visualization of apical and basolateral exocytosis as well as sequential ZG-ZG fusions. Combined with spinning disk microscopy, this assay allows 3D live exocytosis imaging with high temporal and spatial resolution. This novel imaging assay will be useful in visualizing apical, basolateral, sequential, and lateral fusion events for future acinar studies.
Long Term Effects of Early Embryonic Ethanol Exposure, on Behavioural Performance and Learning in Zebrafish, Danio rerio
Keywords: Fetal Alcohol Syndrome (FAS)
Fetal Alcohol Spectrum Disorders (FASDs)
Zebrafish
Learning

Background: Fetal alcohol syndrome (FAS) is a devastating disorder whose mechanisms may be best investigated using animal models. Here we present a novel zebrafish FAS model to investigate the effects of low to moderate alcohol exposure during early development on learning. Methods: At 24-hours postfertilization zebrafish embryos were exposed to low doses of ethanol (external concentrations = 0.00, 0.25, 0.50, 0.75 and 1.00% vol/vol) for a very short duration (2 hours). Upon adulthood associative learning in the zebrafish was tested in a plus maze. Results: This exposure led to no gross anatomical abnormalities or increased morbidity or mortality. Overall activity was not significantly affected by embryonic ethanol exposure. A trend towards a dose-dependent decrease in learning and memory performance was observed. Conclusions: We suggest that zebrafish will be an appropriate model with which one can analyze the behavioural effects of embryonic alcohol exposure and the mechanisms of the ensuing abnormalities.
Enhancing Performance of Vulnerability-based Intrusion Detection Systems
Keywords: Security
Intrusion Detection
Matching
MPDU
Vulnerability
Conficker
IDS
Snort

The accuracy of current intrusion detection systems (IDSes) is hindered by the limited capability of regular expressions (REs) to express the exact vulnerability. Recent advances have proposed vulnerability-based IDSes that parse traffic and retrieve protocol semantics to describe the vulnerability. Such a description of attacks is analogous to subscriptions that specify events of interest in event processing systems. However, the matching engine of state-of-the-art IDSes lacks efficient matching algorithms that can process many signatures simultaneously. In this work, we place event processing in the core of the IDS and propose novel algorithms to efficiently parse and match vulnerability signatures. Also, we are among the first to detect complex attacks such as the Conficker worm which requires correlating multiple protocol data units (MPDUs) while maintaining a small memory footprint. Our approach incurs neglibile overhead when processing clean traffic, is resilient to attacks, and is faster than existing systems.
Efficiency and Emissions Study of a Residential Micro–cogeneration System Based on a Stirling Engine and Fuelled by Diesel and Ethanol
Keywords: Stirling engine
Cogeneration
Ethanol

This study examined the performance of a residential micro–cogeneration system based on a Stirling engine and fuelled by diesel and ethanol. An extensive number of engine tests were conducted to ensure highly accurate and reproducible measurement techniques. Appropriate energy efficiencies were determined by performing an energy balance for each fuel. Particulate emissions were measured with an isokinetic particulate sampler, while a flame ionization detector was used to monitor unburned hydrocarbon emissions. Carbon monoxide, nitric oxide, nitrogen dioxide, carbon dioxide, water, formaldehyde, acetaldehyde and methane emissions were measured using a Fourier transform infrared spectrometer. When powered by ethanol, the system had slightly higher thermal efficiency, slightly lower power efficiency and considerable reductions in emission levels during steady state operation. To further study engine behaviour, parametric studies on primary engine set points, including coolant temperature and exhaust temperature, were also conducted.
The Fates of Vanadium and Sulfur Introduced with Petcoke to Lime Kilns
Keywords: pulp and paper
petroleum coke
vanadium

Petroleum coke (petcoke) has been burned at kraft pulp mills to partially substitute for natural gas and fuel oil used in lime kilns. Due to the high vanadium and sulfur contents in petcoke, there had been concerns over the impact of burning petcoke on kiln and chemical recovery operations. Laboratory studies were performed to examine the fate of vanadium and sulfur in lime kilns and chemical recovery cycle. The results suggest that most of the vanadium in petcoke quickly forms calcium vanadates with lime in the kiln, mostly 3CaO•V2O5. In the causticizers, calcium vanadates react with Na2CO3 in green liquor to form sodium vanadate (NaVO3). Due to its high solubility, NaVO3 dissolves in the liquor circulating around the chemical recovery system. V becomes enriched in the liquor, leading to vanadium build-up in the system. The S in petcoke would stay in the reburned lime, lower the lime availability, increase SO2 emissions from the kiln stack, alter the S balance, increase the liquor sulphidity, and potentially contribute to ring formation in the kiln.
EphA4 Receptor Tyrosine Kinase and PAK1 Signaling: Novel Regulators of Xenopus laevis Brachyury Expression and Involution Movements during Gastrulation
Keywords: Xenopus laevis
Gastrulation
EphA4
Brachyury
PAK1
Involution

Gastrulation is a highly complex series of cellular rearrangements that leads to the internalization of the mesoderm and endoderm. The cellular behaviors that underlie morphogenesis are dependent upon changes in cell motility and polarity. Eph receptors belong to a family of receptor tyrosine kinases that are involved in a variety of developmental processes. This study is the first to examine the role EphA4 during Xenopus gastrulation. Morpholino oligonucleotide (MO) mediated knockdown of EphA4 resulted in attenuated mesoderm involution and reduced the expression of the posterior mesoderm marker brachyury (Xbra). Expression of EphA4 in the blastocoel roof was sufficient to promote ectopic Xbra expression. I show that EphA4 can regulate Xbra expression and involution movements by signaling through PAK1. Temporal regulation of Xbra was sufficent to rescue EphA4 induced gastrulation defects. This study has uncovered a novel EphA4/PAK1 pathway which is required for mesoderm involution and Xbra expression during Xenopus gastrulation.
Solvent Refining of Metallurgical Grade Silicon Using Iron
Keywords: Metallurgical Grade Silicon
Solar Grade Silicon
Solvent Refining
Heavy Medium
Physical Separation
Gettering

Purification of metallurgical grade silicon (MG- Si) by a combination of solvent refining and physical separation has been studied. MG-Si was alloyed with iron and solidified under different cooling rates to grow pure Si dendrites from the alloy. The Si dendrites and FeSi2 that were formed after solidification were then separated by a gravity-based method. The separation method relies on significantly different densities of Si and FeSi2, and uses a heavy liquid with specific gravity between the two phases to float the former on the surface of a heavy liquid, while the latter sinks to the bottom. The effect of particle size and cooling rate on the Si yield and separation efficiency of the Si phase was investigated. The floated Si particles were further purified by removing the physically adherent Fe-Si phase, using an acid leaching method. Analysis of the produced silicon indicates that several impurity elements including P and B can be efficiently removed using this simple and low-cost technique.
It Doesn’t Look Odd to Me: Investigating Perceptual Impairments and Eye Movements in Amnesic Patients with Medial Temporal Lobe Damage
Keywords: Memory
Perception
Eye tracking
Amnesia
Hippocampus
Perirhinal cortex

Two amnesic patients with MTL damage that included the hippocampus and perirhinal cortex were tested along controls on a series of “oddity” discrimination tasks, in which they had to select an odd item from a visual array. Participants’ eye moments were monitored while they performed these tasks. Three types of stimuli were used: greebles, scenes, and faces. Results revealed that patients were impaired on tasks that required them to discriminate between items that shared features in common and tasks that required processing items from different viewpoints. An analysis of their eye movements revealed that their impaired performance was linked with decreased viewing times of target items compared to controls, when discriminating between greebles and scenes; their poor performance on the faces task could not be explained by the same token.
Towards a Design Tool for Turbomachinery
Keywords: CFD
Turbine
Navier-Stokes
Finite-Difference
cascade
turbomachinery
approximate-factorization
spalart-allmaras

A two-dimensional thin-layer Navier-Stokes cascade flow solver for turbomachinery is developed. A second-order finite-difference scheme and a second and fourth-difference dissipation scheme are used. Periodic and non-reflecting inlet and outlet boundary conditions are implemented into the approximate-factorization numerical method. Turbulence is modeled through the one-equation Spalart-Allmaras model. A two-dimensional turbomachinery cascade structured grid generator is developed to produce six-block H-type grids. The validity of this work is tested in various ways. A grid convergence study is performed showing the effect of grid density. The non-reflecting inlet and outlet boundary conditions are tested for boundary placement influence. Comparisons of the flow solver numerical results are performed against experimental results. A Mach number sweep and angle of attack sweep are performed on two similar transonic turbine cascades.
Strain and Sex Differences in the Hepatotoxicity of 4-Aminobiphenyl in the Mouse
Keywords: Aromatic amine
Cytotoxicity
4-Aminobiphenyl
Tumorigenesis
4-ABP
Mouse strain
Hepatotoxicity
Gender disparity
Strain disparity
Chemical carcinogenesis
Hepatocellular carcinoma
HCC
Carcinogenesis
ABP

Recent studies from our laboratory on the aromatic amine carcinogen, 4-aminobiphenyl (ABP) have shown a significantly lower prevalence of ABP-induced liver tumors in male mice lacking the N-acetyltransferases, and a dramatically lower prevalence in females than in males, but no association of tumor prevalence with strain or sex differences in levels of acute ABP-induced DNA damage. This thesis aimed to investigate the possible involvement of acute cytotoxic effects of ABP in the development of a tumor-promoting inflammatory environment. We found that wild-type male mice showed higher acute hepatotoxicity to ABP, as well as, a possible trend towards higher serum levels of the pro-inflammatory cytokine interleukin 6. This correspondence between acute ABP cytotoxicity and inflammatory response with ultimate tumor growth is consistent with a model whereby ABP not only initiates cells by damaging DNA but also promotes tumor growth in a gender-selective fashion that may be governed by gonadal hormone influences.
Communication Loss Management and Analysis for Multiple Spacecraft Formation Flying Missions
Keywords: Spacecraft Formation Flying
Synchronization Control
Robots in Formation
Communication Loss Management

This thesis presents a method for managing periods of communication loss between multiple spacecraft in formation flying (MSFF), and analyzes the effects of this method on the stability of the formation keeping control algorithm. The controller of interest in this work in an adaptive nonlinear controller, where synchronization is also incorporated to force the position tracking errors to converge to zero at the same rate. The communication loss compensation technique proposed in this thesis is to use the previously communicated data in lieu of the lost data, which is an effective and computationally-efficient technique that is advantageous for small satellites. The performance parameter of interest in this research is the maximum rate of communication loss that an MSFF system can withstand before going unstable, and this is analyzed theoretically and through simulations. Finally, experiments involving multiple robots in formation with communication loss are conducted, and the results are presented.
Investigating the Relationship between Stride Interval Dynamics, the Energy Cost of Walking and Physical Activity Levels in a Pediatric Population
Keywords: gait
energy cost
activity
stride interval

The strength of time-dependent correlations known as stride interval (SI) dynamics have been proposed as an indicator of neurologically healthy gait. Most recently, it has been hypothesized that these dynamics may be necessary for gait efficiency although the supporting evidence to date is limited. To gain a better understanding of this relationship, this study investigated stride interval dynamics, the energy cost of walking, and physical activity in a pediatric population. The findings indicate that differences in energy cost are not reflected in the stride interval dynamics of able-bodied children. Interestingly, increasing physical activity levels were associated with decreasing variance in stride interval dynamics between subjects, though this finding only approached significance (p=0.054). Lastly, this study found that stride interval dynamics in children as young as nine years were comparable to stride interval dynamics found in healthy young adults.
Effects of Intravesical Botulinum Toxin-A on Bladder Dysfunction and Autonomic Dysreflexia after Spinal Cord Injury: Role of CGRP Primary Afferents and NGF
Keywords: Spinal cord injury
autonomic dysfunction
bladder overactivity
autonomic dysreflexia
Botulinum toxin-A
CGRP
NGF
C afferent fibres

Spinal cord injury (SCI) remains a significant cause for morbidity and mortality in North America. Bladder dysfunction following SCI is very common and could lead to severe complications including renal failure and autonomic dysreflexia (AD). AD involves life threatening episodes of hypertension in patients with SCI above T6 level. Current management protocols for AD are symptomatic and usually ineffective. Botulinum toxin-A (BTX-A), has been successfully used recently in SCI patients because it reduces the detrusor contractility via inhibiting acetylcholine release from efferent nerve endings. Recent evidence, however, suggests a sensory involvement via modulation of sensory neuropeptides, neurotransmitters, and receptors. It is still, however, unclear whether BTX-A can affect putative spinal neurons involved in AD. In this study we demonstrated that intravesical BTX-A treatment has blocked AD in rats with T4-SCI, and also provided a novel mechanism for the control of autonomic dysreflexia via a minimally invasive treatment modality.
Identification of Genes and Putative Regulatory Variants Contributing to Reading Disabilities and Attention Deficit/ Hyperactivity Disorder
Keywords: Reading Disabilities
ADHD

Reading Disabilities (RD) and Attention Deficit/Hyperactivity Disorder (ADHD) are common neurodevelopmental disorders with evidence for shared genetic etiology. This study examined four predicted neuronal migration genes in RD (DCDC2, KIAA0319, DCDC2B and NEDD4L), and three of these genes in ADHD (DCDC2, DCDC2B and NEDD4L). Putative regulatory elements of DCDC2 (6p) and KIAA0319 (6p) were screened to identify functional risk variants that explain previous association findings. No statistically significant associations were observed in DCDC2. In KIAA0319, variants with predicted regulatory function showed association with RD. This supports the hypothesis that causal RD risk variants in KIAA0319 alter gene expression. DCDC2B (1p), the homolog of DCDC2, showed suggestive evidence for association to ADHD, but not RD. Previous association findings in NEDD4L (18q) could not be replicated. No pleiotropic gene for RD and ADHD was identified. However, together with previous findings, this study supports that neuronal migration may be a common underlying deficit in both RD and ADHD.
Identification of Candidate Genes for Neuropathic Pain at the Pain1 Locus on Mouse Chromosome 15
Keywords: Neuropathic Pain
Gene

Sciatic and saphenous neurectomy produces in mice a neuropathic pain-like behaviour (‘autotomy’). A/J mice express higher autotomy levels than C57BL6/J mice. A previous study used autotomy data for these strains and their 23 recombinant daughter inbred lines of the AXB-BXA set, to map a quantitative trait locus (QTL) for autotomy on chromosome 15. Since then, this QTL, named Pain1, was replicated twice. Since all three studies used a low-resolution genetic map based on microsatellites its confidence length precluded identification of candidate gene(s). To overcome this problem, I used a higher resolution SNP-based genetic map and refined Pain1’s peak location, identifying in it 80 candidate genes. But only Lynx1, Arc and Sharpin had sequence mismatches between A/J and C57BL6/J, known neural functions, and contrasting expression levels in DRGs and spinal cord of intact, sham-operated, and neurectomized mice of these lines. Meeting these criteria made them our best candidate genes for autotomy.
Metoprolol Impairs Mesenteric and Posterior Cerebral Artery Function in Mice
Keywords: mesenteric resistance artery
beta-blockers
metoprolol
beta-adrenergic receptor
posterior cerebral artery
isoproterenol

Background/Rationale: In addition to their established cardioprotective role, β-adrenergic antagonists also increase the risk of stroke and mortality. We propose that a vascular mechanism could contribute to cerebral tissue ischemia in β-blocked patients. Methods: Cardiac output (CO), mean arterial pressure (MAP) and microvascular brain oxygen tension (PBrmvO2) were measured in anesthesized mice treated with metoprolol (3mg•kg-1, i.v.). Dose-response curves (DRCs) for adrenergic-agonists were generated in mesenteric resistance arteries (MRAs; isoproterenol, clenbuterol) and posterior cerebral arteries (PCAs; phenylephrine, isoproterenol) before and after metoprolol treatment. Results: Metoprolol reduced CO, maintained MAP and increased systemic vascular resistance (SVR) resulting in a decreased PBrmvO2 in mice. Metoprolol attenuated β-adrenergic mediated vasodilation in both MRAs and PCAs. Conclusions: Metoprolol reduced brain perfusion in mice. A decrease in CO contributed however, metoprolol also inhibited β-adrenergic vasodilation of mesenteric and cerebral arteries. This provides evidence in support of a vascular mechanism for cerebral ischemia in β-blocked patients.
Planar Photonic Crystals for Biosensing
Keywords: photonic crystals
biosensing

In this thesis, planar photonic crystals for optofluidic biosensing applications are analyzed. Planar photonic crystals are optically resonant structures which possess modal characteristics which can be exploited for biosensing applications. Sensing is achieved by detecting changes in refractive index due to analyte interactions in a sampled fluid. This work describes a broad study of photonic crystal slab sensors, with special consideration to biosensing. Outlined are considerations pertaining to sensing figures of merit, device fabrication, and performance. Results of simulations and device characterization indicate that planar photonic crystals possess sensing attributes similar or better than existing optically resonant refractive index sensors, such as surface plasmon resonance, grating, and interferometric waveguide sensors. Additionally, these photonic crystals can be patterned in large-areas which enable a simple light coupling scheme. All considered, their appeal as a biosensing solution is justified in the area of in vitro diagnostics.
Energy-based Error Control Strategies Suitable for Long MD Simulations
Keywords: Molecular Dynamics
Numerical Analysis
Simulation
Error Control

When evaluating integration schemes used in molecular dynamics (MD) simulations, energy conservation is often cited as the primary criterion by which the integrators should be com- pared. As a result variable stepsize Runge-Kutta methods are often ruled out of consideration due to their characteristic energy drift. We have shown that by appropriately modifying the stepsize selection strategy in a variable stepsize RK method it is possible for the MD practitioner to obtain substantial control over the energy drift during the course of a simulation. This ability has been previously unreported in the literature, and we present numerical examples to illustrate that it can be achieved without sacrificing computational efficiency under currently obtainable timescales.