VictorJuiz/thesis huggingface dataset:
Development of a Phased Array Focused Ultrasound Transducer for Two-photon Microscopy Guided Neural Studies

Focused ultrasound combined with intravenously injected microbubbles is a promising non-invasive therapy capable of temporarily disrupting the blood-brain barrier for targeted drug delivery. Established in vivo experiments on rodent models combine focused ultrasound treatment with two-photon microscopy imaging to improve understanding of microvasculature response. A phased array, an advanced ultrasound therapy device, was successfully developed to improve pressure transmission in these experiments. An investigation of transducer sensitivity to setup equipment suggested modifications to setup procedures, for example recording objective position, may improve in situ pressure estimates. A ring array composed of 50 lateral mode elements, geometry determined by pressure field simulations, was successfully fabricated. Fibre optic hydrophone pressure field measurements confirmed the device had an appropriate focal size (0.7mm diameter x 4mm axial length) and reached therapeutic pressure levels (>0.5MPa). Ex vivo transcranial measurements demonstrated moderate focal correction and off-axis steering capabilities that may improve experimental throughput and target alignment.

Keywords: Focused ultrasound
Transducer
Lateral mode
Hydrophone
Phased array
Blood-brain barrier
Advisor: Hynynen, Kullervo
Bubble Formation in a Horizontal Channel at Subcooled Flow Condition

Bubble nucleation at subcooled flow boiling condition in a horizontal annular channel with a square cross section by the use of high-speed camera is investigated. The channel represents a scaled-down version of a single rod of CANDU reactor core. The experiments were performed by the use of water at pressures between 1-3 atm, constant heat flux of 0.124 MW/m2, liquid bulk subcooling of 32-1oC and mean flow velocities of 0.3-0.4 m/s. Bubble lift-off diameters were obtained from direct high speed videography. The developed model for the bubble lift-off diameter was obtained by analyzing the forces acting on a bubble. Furthermore, a model for the bubble growth rate constant was suggested. The proposed model was then compared to experimental data and it has shown a good agreement with the experimental data. Additionally, the effects of liquid bulk subcooling, liquid pressure and mean flow velocity on bubble lift-off diameter were investigated.

Keywords: Subcooled two phase flow
Bubble nucleation
Critical Heat Flux
Heat transfer
Advisor: Nasser, Ashgriz
The Impact of Achieving Low Disease Activity in the First Year of Disease on Future Disability and Damage in Early Rheumatoid Arthritis

Aim: To describe the predictive validity of reaching low disease activity (LDA) at 1 year on future disability and joint damage in patients with early rheumatoid arthritis (ERA). Methods: First a systematic literature review of prognostic studies assessing the association between disease activity and functional or radiographic outcomes in ERA was performed. Then data from the Study Of New-Onset RA (SONORA) were used to evaluate the impact of year-one LDA on 3-year disability and 2-year radiographic progression using multivariate regression analyses. Results: Our review demonstrated evidence for relationship between baseline disease activity and future disability and join damage. However evidence for the impact of early treatment response on long-term outcomes in ERA is sparse. Analysis of 984 patients showed year one LDA predicts lower HAQ (p<.0001) and less damage (p=0.04) in future. Conclusion: Reaching LDA early is associated with better long-term functional and radiographic outcomes in patients with early RA.

Keywords: prognosis
outcome
rheumatoid arthritis
disability
joint damage
Advisor: Bombardier, Claire
Physiological and Psychological Stress Markers in Concussed Athletes from Injury to Post-return to Play

Introduction: Concussions are a physiologically & psychologically stressful event. Stress markers may provide insight into concussion recovery, but have not been examined. Purpose & Method: To investigate the stress response of concussed athletes compared to controls from injury to post-RTP. Concussed athletes’ Mood states, Perceived Stress, HRV, and Morning & Afternoon Cortisol were assessed at 3 phases of recovery following concussion. Results: Repeated measures ANOVA revealed significant interactions for TMD, Depression, Anger, Confusion, Fatigue, HF norm (rest), LF norm (rest), HF norm (difference between sitting & standing), LF norm (difference between sitting & standing), and LF/HF ratio (difference between sitting & standing). Vigor & Tension demonstrated significant changes over time in the concussed group. Significant difference between the two groups for morning Cortisol levels at phase 3 was revealed. Conclusion: Concussed athletes display elevated levels of stress post-injury. Findings warrant further investigation of stress markers in concussed athletes during recovery.

Keywords: concussion
stress
Heart Rate Variability
HRV
Cortisol
Mood
Advisor: Mainwaring, Lynda
Design of a Peripheral Nerve Electrode for Improved Neural Recording of the Cervical Vagus Nerve

Vagus nerve stimulation (VNS) is an approved therapy for patients suffering from refractory epilepsy. While VNS is currently an open loop system, making the system closed loop can improve the therapeutic efficacy. Electrical recording of peripheral nerve activity using a nerve cuff electrode is a potential long-term solution for implementing a closed-loop controlled VNS system. However, the clinical utility of this approach is significantly limited by various factors, such as poor signal-to-noise ratio (SNR) of the recorded electroneurogram (ENG). In this study, we investigated the effects of (1) modifying the electrode contact dimensions, (2) implementing an external shielding layer on the nerve cuff electrode and (3) exploring shielded bipolar nerve cuff designs on the recorded ENG. Findings from both computer simulations and animal experiments suggest that significant improvements in peripheral nerve recordings can be achieved.

Keywords: nerve cuff electrode
vagus nerve stimulation
Advisor: Yoo, Paul B.
Development of a Methodology for the Examination of Conductance Densities and Distributions of Hippocampal Oriens-lacunosum/moleculare Interneurons using Ensemble Modelling

The hippocampus is a brain region that is critically involved in memory formation. Stratum oriens-lacunosum/moleculare (O-LM) interneurons have been shown to modulate incoming sensory information onto principal cells in CA1. Multi-compartment computational models of O-LM cells have been developed to better understand their functional roles in network contexts. Due to the variability and incompleteness of experimental details, however, a population of models that collectively captures intrinsic O-LM cell behavior is needed. We generated a database of O-LM models with physiologically plausible ranges for conductance densities using NEURON simulations on a supercomputer cluster. A subset of models that best represented O-LM cell electrophysiological output was subsequently extracted from the database and analyzed in order to determine correlations in conductance densities. Three major co-regulatory balances were found, which provide specific hypotheses for experimental investigations and point to the possibility of identifying a “signature” of conductance density balances for particular neuronal cell types.

Keywords: computational
neuroscience
Advisor: Skinner, Frances
Coordinated Post-transcriptional Regulation by MicroRNAs and RNA- binding Proteins

Both microRNAs (miRNAs) and RNA-binding proteins (RBPs) regulate post- transcriptional events, but the post-transcriptional contribution to the global mammalian transcriptomes is still not well understood. In this study we study the synergistic interaction between microRNAs that inhibit gene production, and a special RBP, HuR, that positively regulates mRNA stability. We examined their relationship in terms of spatial, conservational and expressional perspective. We show comprehensive mapping of HuR binding sites by combination of its structural and sequential preferences; and cross-platform normalization method within a process of refining miRNA and HuR binding site mapping. Finally, we observed co-evolution of miRNA and HuR binding sites by looking at their proximity and conservation levels. Collectively, our data suggest that mammalian microRNAs and HuR, with seemingly opposing regulatory effects, cooperatively regulate their mutual targets.

Keywords: microRNA
HuR
RNA-binding protein
evolution
post-transcriptional regulation
RNA-seq
normalization
Advisor: Zhang, Zhaolei
Wrana, Jeffrey
The Enzymology of Fetuin: A Potential Link Between Periodontal Diseases and Calcifying Atheromas

Periodontal diseases may increase risk of vascular calcification in cardiovascular diseases but the potential mechanisms are not defined. Fetuin, a naturally-occurring serum glycoprotein in humans, protects against ectopic arterial calcification. We considered that patients with periodontitis could be at increased risk of developing calcifying atheromas because periodontal-disease associated enzymes may enter the circulation and subsequently degrade fetuin, thereby disrupting its ability to inhibit calcification. By in silico investigation, MMP -3 and -7 were predicted to cleave fetuin but only MMP-7 actually degraded human fetuin in vitro. MMP-7 degradation of fetuin was time- and concentration- dependent and was inhibited by an MMP Inhibitor. By mass spectrometry the presence of novel, MMP-7-mediated cleavage sites in fetuin were found. Fetuin bound tightly to MMP-7 (kd =2.96 x 10-9 M). The degradation of fetuin by MMP-7 could explain, at least in part, the apparent association between periodontal diseases and calcifying atheromas.

Keywords: fetuin
periodontitis
cardiovascular disease
calcifying atheroma
biochemistry
matrix metalloproteinase
Advisor: McCulloch, Christopher
Tenenbaum, Howard
Adherence to Home Based Cardiac Rehabilitation

Cardiac rehabilitation (CR) is recommended for those living with heart disease, however adherence is suboptimal. The home program (HP) model of care is as clinically effective as traditional programs (TP), however little information exists about the HP&rsquo;s effect on adherence. The objectives of this thesis were to 1) compare adherence of patients in a HP and TP model of CR. 2) To characterize self-regulatory self-efficacy (SR-SE) in a CR HP and 3) to explore the reasons for non-completion of a HP. Study 1 showed adherence to be similar between the TP and HP. Study 2 showed that SR-SE was high throughout the HP for completers, but dropped in those who did not complete the program. The HP is a good alternative for those unable to attend a TP; however those with low SR-SE may require further interventions to help them complete their program.

Keywords: Cardiac Rehabilitation
Home Program
Advisor: Brooks, Dina
Pharmacogenetic Inhibition of the Subcoeruleus Region Influences REM Sleep and Cataplexy in Narcoleptic Mice

Introduction: Cataplexy - the sudden involuntary loss of skeletal muscle tone – is a defining feature of narcolepsy. The current study aimed to determine if cataplexy is influenced by direct manipulation of REM sleep circuitry. We did this by pharmacogenetically inhibiting the REM sleep center, subcoeruleus (Sub-C). Methods: Inhibitory DREADD (hM4D-Gi) was bilaterally targeted to the Sub-C in hypocretin knockout mice (n=7). Intraperitoneal administration of clozapine-n-oxide was used to inhibit Sub-C cells expressing hM4D-Gi. Electrophysiological and behavioral criteria were used to characterize cataplexy and REM sleep. Results: Sub-C inhibition increased REM sleep and cataplexy amounts (p<0.05). Sub-C inhibition increased time spent in cataplexy amounts by increasing the number of cataplexy attacks (p<0.05). This intervention triggered increases in basal muscle tone during REM sleep, but had negligible effects on muscle tone during cataplexy (p>0.05). Conclusion: Pharmacogenetic manipulation of the Sub-C suggest that REM sleep and cataplexy are mediate by similar neural mechanism.

Keywords: Sleep
REM Sleep
subcoeruleus
cataplexy
narcolepsy
Advisor: Peever, John H.
The Role of Syk in Airway Hyperresponsiveness and Remodeling in House Dust Mite Induced Murine Models of Allergic Airways Inflammation

Spleen tyrosine kinase (Syk) plays a critical role in regulation of immune and inflammatory responses. This thesis investigated the role of Syk in the development of the asthma phenotype in acute and chronic mouse models of allergic airways inflammation. Airway hyperresponsiveness (AHR) to methacholine and inflammation increased significantly in HDM-induced compared with the saline control mice. We demonstrated that in vivo inhibition of Syk by selective Syk inhibitors, and genetic deletion of Syk using conditional Syk knockout mice attenuated AHR despite of inflammatory cell influx in the lung. Histological analysis showed airway remodeling in the chronic model, which was attenuated to some degree by deletion of Syk. This study identified a role of Syk in airway hyperresponsiveness and remodeling without significantly affecting leukocyte recruitment in HDM model of airways disease. My results support the improvement of therapeutic strategies in asthma by targeting the Syk pathway.

Keywords: Allergic Airway Inflammation
Airway Hyperresponsiveness
House Dust Mite
Murine Model
Advisor: Chow, Chung-Wai
Characterization of an Iron-Sulfur Binding Protein in the Tail Tip Complex of Bacteriophage Lambda

The assembly of λ tail requires the action of 11 gene products which must interact in an organized fashion to assemble infectious tail particles. GpL is an essential protein for the formation of the tail tip complex and necessary for the assembly of λ tail. The work described here has shown that gpL and its homologues contain two domains where the C-terminal domain coordinates an oxygen-sensitive [4Fe-4S] 2+ cluster using 4 highly conserved cysteines. This is the first report of a bacteriophage morphogenetic protein to coordinate a [4Fe-4S]2+ cluster. Through two individual cysteine mutants, C184A and C228A, it was determined that these mutant proteins coordinate a [2Fe-2S]2+ cluster also using 4 cysteines; the fourth cysteine being non-conserved. λ tails assembled with cysteine mutant gpL resulted in a 1000-fold decrease in the titer of active tails and tail particles could not be detected by TEM indicating that λ tails cannot be assembled with cysteine mutant gpL. I propose that the coordination of a [4Fe-4S] cluster with the four conserved cysteines maintains a conformation in gpL that can optimally interact with other tail proteins for efficient tail assembly.

Keywords: bacteriophage
lambda
iron-sulfur cluter
protein assembly
Advisor: Davidson, Alan R.
Effect of Early Life Vitamin D Supplementation on Bone Development

Vitamin D is important for bone development with immunomodulatory effects. This study investigated whether feeding CD-1 and interleukin 10 (IL-10) knockout (KO) dams low (25 IU/kg diet) or high (5,000 IU/kg diet) vitamin D affected bone health of dams as well as their offspring. Offspring were weaned to 1 of the 2 diets and followed to young adulthood. Unlike CD-1 dams, IL-10 KO dams experienced greater femur strength with high vitamin D. CD-1 male offspring had reduced femur neck strength and female offspring had smaller, weaker femurs, and weaker lumbar vertebra 2 (LV2) with high maternal vitamin D. IL-10 KO male offspring had larger femurs and female offspring had stronger femurs when weaned to high vitamin D. Low vitamin D did not adversely impact bone health but the optimal level of dietary vitamin D seems to differ between healthy and inflammatory states.

Keywords: intervention study
early programming
vitamin D
bone development
inflammatory bowel disease
CD-1 mice
IL-10 KO mice
Advisor: Ward, Wendy
Elucidating the Role of gpW: an Essential Baseplate Protein in Bacteriophage P2

The long, contractile tails of myophages are the conduit for phage DNA transfer into the bacterial host cell and the most important part of the myophage tail is the baseplate; a complex structure, distal to the phage head. To better understand the structure and function of myophage baseplates, a component of the phage P2 baseplate, gpW was studied. This protein is widely conserved among myophages and is essential for the formation of infectious phage particles. Bioinformatic work confirmed that gpW homologues are found in almost all myophages and in many prophages. Moreover, gpW was shown to be a structural component of the virion; and, using electron microscopy, it was found to be at the top of the P2 baseplate. It was also found that some single residue substitutions can completely disrupt gpW function. Finally, evidence is presented that at least eight different proteins may be required to form intermediate P2 baseplate structures while other proteins may be necessary for the formation of stable baseplate complexes.

Keywords: Bacteriophage
Baseplate
Phage P2
gpW
Myophages
Phage Assembly
Advisor: Davidson, Alan R.
Reprogramming Mouse Glioma Stem Cells with Defined Factors

This thesis shows that p53-deficient mouse glioma brain tumour stem cells (BTSCs), which fail to express pluripotency factors, can be reprogrammed with specific transcription factors to generate iPS cell lines (GNS-iPS) expressing endogenous pluripotency factors (Nanog, Oct4, and Rex1). GNS-iPS cell lines formed embryoid bodies (EBs) in vitro and undifferentiated growths in vivo that phenotypically did not resemble tumours derived from non-reprogrammed BTSCs. EBs formed from one GNS-iPS cell line expressed markers of mesoderm, endoderm, and ectoderm. Tumours produced from GNS-iPS cells had reduced astrocytic marker (GFAP) expression compared to those generated from control iPS cell lines or non-reprogrammed BTSCs. Preliminary results suggest that the reprogrammed cells can be re-differentiated into cells that show neural precursor phenotype. These findings suggest that BTSCs can acquire aspects of the pluripotent state with a defined set of transcription factors, opening the door for further exploration of reprogramming strategies to attenuate the cancer phenotype.

Keywords: cancer
glioma
reprogramming
stem cells
iPS
Advisor: Dirks, Peter Benjamin
Repulsive-force Electrostatic Actuated Micromirror for Vector-based Display Systems

This thesis presents the design and development of a novel two-axis micromirror utilizing electrostatic, repulsive-force rotational actuators for laser scanned vector display systems. The micromirror consists of a 1.0 mm reflective mirror plate that can be rotated at high speeds to steer a laser beam to generate images. Fabricated using PolyMUMPs, the micromirror is operated in a non-resonant mode between 0 V and 200 V and can achieve a maximum optical scanning angle of ±2.6° in each axis with a settling time as fast as 2.75 ms and a first resonant frequency of 1400 Hz. Open-loop control methods were developed for image correcting and improving image quality. The micromirror was integrated into a portable, handheld vector display device which included designing and developing driving circuits, device firmware, mechanical components and optical components.

Keywords: Micromirror
Repulsive-Force
Electrostatic Actuator
Vector Display
Advisor: Mrad, Ridha Ben
He, Siyuan
SLIT2 Prevents Renal Ischemia Reperfusion Injury in Mice

The Slit family of secreted proteins act as axonal repellents during embryogenesis. Slit2 via its receptor, Roundabout-1, also inhibits chemotaxis of multiple leukocyte subsets. Using static and microfluidic shear assays, we found that Slit2 inhibited multiple steps required to recruit circulating neutrophils. Slit2 blocked capture and firm adhesion of human neutrophils to and transmigration across inflamed primary vascular endothelial cells. To determine the response of Slit2 in renal ischemia reperfsuion injury, Slit2 was administered prior to bilateral renal pedicle clamping in mice. This led to significant decreases in both renal tubular necrosis score and neutrophil infiltration. Administration of Slit2 also prevented elevation of plasma creatinine following injury in a dose-dependent manner. Furthermore, administration of Slit2 did not increase hepatic bacterial load in mice infected with L.monocytogenes infection. Collectively, these data demonstrate Slit2 as an exciting therapeutic molecule to combat renal ischemia reperfusion injury without compromising protective host innate immune functions.

Keywords: acute kidney injury
ischaemia-reperfusion injury
Advisor: Robinson, Lisa
A Fault-tolerant Strategy for Embedded-memory SoC OFDM Receivers

The International Technology Roadmap for Semiconductors projects that embedded memories will occupy increasing System-on-Chip area. The growing density of integration increases the likelihood of fabrication faults. The proposed memory repair strategy employs forward error correction at the system level and mitigates the impact of memory faults through permutation of high sensitivity regions. The effectiveness of the proposed repair technique is demonstrated on a 19.4-Mbit de-interleaver SRAM memory of an ISDB-T digital baseband OFDM receiver in 65-nm CMOS. The proposed technique introduces a single multiplexer delay overhead and a configurable area overhead of M/i bits, where M is the number of memory rows and i is an integer from 1 to M, inclusive. The proposed strategy achieves a measured 0.15 dB gain improvement at a 2e-4 Quasi-Error-Free (QEF) BER in the presence of memory faults for an AWGN channel.

Keywords: Fault-Tolerance
Embedded-Memory
System-on-Chip
Baseband Signal Processing
Advisor: Gulak, P. Glenn
Organogenesis in Vitro under Altered Auxin Signaling Conditions

The ratio of auxin to cytokinin determines de novo organogenesis in plants. Relatively little is known about the effect of genetically altered auxin signaling on in vitro organogenesis. Here, callusogenesis, shoot, and root formation were studied in loss- (LOF) and gain-of-function (GOF) alleles in two phylogenetically related Auxin Response Factors (ARFs), MONOPTEROS (MP/ARF5) and NON-PHOTOTROPHIC HYPOCOTYL 4 (NPH4/ARF7). Reduced MP activity greatly diminished shoot regeneration, and partially diminished callusogenesis and root formation. LOF in NPH4 strongly decreased callusogenesis, and mildly decreased shoot and root regeneration in particular categories of explants. By contrast, organogenesis responses were strongly increased in aerial explants carrying the GOF transgene dMP. Thus, both MP and NPH4 seem to act as positive regulators of certain organogenesis processes and the GOF dMP transgene may be of interest for stimulating organogenesis in plant species with poor regeneration properties. Also, organogenesis in vitro may reveal unknown developmental ARF functions.

Keywords: auxin signaling
auxin
cytokinin
auxin response factors (ARFs)
callus
de novo organogenesis
shoot regeneration
MONOPTEROS (MP/ARF5)
NON-PHOTOTROPHIC HYPOCOTYL4 (NPH4/ARF7)
Arabidopsis thaliana
Advisor: Berleth, Thomas