VictorJuiz/thesis huggingface dataset:
Utilizing Positron Emission Tomography in Lung Cancer Treatment
Keywords: optimization
robust
radiation therapy
IMRT
lung cancer
machine learning

We explore both robust biologically guided intensity-modulated radiation therapy (BG-IMRT) and pattern recognition to identify responders to cancer treatment for lung cancer. Heterogeneous dose prescriptions that are derived from biological images are subject to uncertainty, due to potential noise in the image. We develop a robust optimization model to design BG-IMRT plans that are de-sensitized to uncertainty. Computational results show improvements in tumor control probability and deviation from prescription dose compared to a non-robust model, while maintaining tissue dose below toxicity levels. We applied machine learning algorithms to 4D gated positron emission tomography/computed tomography (PET/CT) scans. We identified classifiers which could outperform a naive classifier. Our work shows the potential of using machine learning algorithms to predict patient response. This could hopefully lead to more adaptive treatment plans, where the clinician would adapt the treatment based on the prediction provided at certain time intervals in the treatment.
Design of a Haptic Simulator for Pedicle Screw Insertion in Pediatric Scoliosis Surgery
Keywords: Haptics
Robotics
Training Simulator
Virtual Reality
Pedicle screw insertion
orthopedic surgery
spine surgery

The following work presents the design of a haptic training simulator for pedicle screw insertions in pediatric scoliosis surgery. In particular, the haptic simulator simulates the haptic sensations associated with probe channeling through the pedicle using the free-hand technique. The design includes 1 DOF custom haptic device, haptic model, and controller. The design is tested and evaluated for feasibility through a small pilot studying involving 5 expert surgeons. Significant agreement across expert surgeons was obtained regarding the feasibility and potential for the simulator to be a useful training tool.
Alternatives to Decentralization of Pharmaceutical Policies in Brazil: Case Studies of HIV/AIDS and Tuberculosis
Keywords: health care system
public health
pharmaceutical policy
decentralization

Increasing attention has been paid to decentralized health care systems in order to evaluate health outcomes. In Brazil, state-run pharmaceutical assistance falls within the scope of a decentralized health care system, also known as SUS (Brazilian Unified Health System). The research intends to shed light on pharmaceutical policy implementation in Brazil through SUS, and argues that it can be used as a guide for institutional reform. This will be accomplished by reviewing the weaknesses and strengths of the SUS decentralized structure as revealed in the pharmaceutical policy responses to HIV/AIDS and tuberculosis. Under the assumption of pharmaceutical assistance improvement conditioned to re-centralization of some functions; it can be argued that a balanced approach to decentralization is more desirable to the pharmaceutical sector than the existing decentralized system. The aim of this study is to highlight the advantages of establishing a hybrid system for pharmaceutical assistance.
Depoliticizing the United Nations Human Rights Council: Mixed Membership for a Brighter Future
Keywords: Human Rights Council
Politicization
International Law
human rights

The United Nations charter-based human rights apparatus has long been plagued by concerns of politicization. This pervasive issue first brought the demise of the United Nations Commission on Human Rights in 2006 and led to the creation of an entirely new entity, the United Nations Human Rights Council, in the hope of answering the concerns of the international community. Although major reforms were undertaken, politicization is now once again cited as one of the main issues of the new Council. In this essay, we identify the source of politicization as the intergovernmental nature of these human rights bodies, and suggest that mitigation of this issue is possible through the reform of the Council’s membership. The creation of a mixed expert-state body will allow for a more functional, depoliticized body in the protection and promotion of human rights.
Structural and Biochemical Characterization of CRISPR-associated Cas4 Nucleases from a Prokaryotic Defense System
Keywords: CRISPR, Cas4, nuclease, [4Fe-4S] cluster

Nucleases are an essential component of the prokaryotic CRISPR-Cas immunity as well as repair mechanisms within prokaryotic organisms. To better understand the adaptation step of CRISPR-Cas immunity, I have characterized three Cas4 proteins from hyperthermophilic archaea: SSO0001 and SSO1391 from Sulfolobus solfataricus and Pcal_0546 from Pyrobaculum calidifontis. All three proteins have metal-dependent 5′ to 3′ exonuclease and endonuclease activities, while SSO1391 also demonstrates 3′ to 5′ exonuclease activity. Site-directed mutagenesis confirmed that the conserved RecB motif residues are important for the nuclease activity in all three proteins. SSO0001 and Pcal_0546 also exhibit ATP-independent unwinding and cleavage of splayed arm substrates. Structural analysis of SSO0001 showed it is a toroidal decamer with a [4Fe-4S] cluster and Mn2+ ion bound in the active site located inside the internal tunnel. Our results show that Cas4 proteins have the ability to create 3'-DNA overhangs which may contribute to the addition of novel CRISPR spacers.
The Role of Stretch-induced Myometrial Cytokines in Leukocyte Recruitment during Parturition
Keywords: labour
stretch
cytokine
leukocyte
myometrium

Spontaneous term labour is associated with increased inflammatory events in the myometrium including cytokine production and leukocyte infiltration. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte transendothelial migration into the term pregnant myometrium through the release of various cytokines. The current study demonstrated that static mechanical stretch directly induces secretion of multiple cytokines and chemokines by human myometrial smooth muscle cells. Stretch-induced cytokines (1) increased vascular permeability; (2) enhanced leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by (3) inducing the expression of endothelial cell adhesion molecules; and (4) directed the transendothelial migration of peripheral neutrophils. Our data provide a direct proof of mechanical regulation in leukocyte recruitment from the uterine blood vessels, which represents a putative mechanism for the leukocyte infiltrate seen in the myometrium during labour and postpartum involution.
Perceptions about Crime and Safety in the Region of Peel: A Qualitative Assessment of Connections between the Social and Built Environment and Crime in Three Neighbourhoods
Keywords: geography
social capital
social cohesion
neighbourhood
community
social disorganization theory
social environment
built environment

This thesis investigated the role that local environmental factors play in influencing perceptions of crime and safety across three neighbourhoods within the Region of Peel, Ontario. Semi-structured interviews were conducted with local experts to examine their perceptions of crime and safety, and elements of the built and social environment that may influence these perceptions and identified dimensions of social capital that serve as pathways through which broader environmental determinants of crime and safety can become embedded at the local neighbourhood level. Findings of this research revealed that the perceived relationships between the social and built environment and crime are complex and that dimensions of social capital such as informal social ties serve as a mediator between the environment and perceptions about crime and how perceived and actual crime may be reduced by modifying elements of the built and social environment in order to strengthen local dimensions of social capital.
Therapeutic Peptide-functionalized Gold Nanoparticles for the Treatment of Acute Lung Injury
Keywords: acute lung injury
gold nanoparticle
peptide
drug delivery
protein kinase C delta
lung transplant

Acute lung injury (ALI) is a major cause of mortality after lung transplantation. Recent studies indicate protein kinase C delta (PKCδ) could be an effective target to treat ALI. We have developed a gold nanoparticle (GNP)-peptide hybrid that can inhibit PKCδ signaling. PKCδ inhibitor peptide (PKCi) and 95P2P4 stabilizing peptides were conjugated onto GNP. Physicochemical properties of the nanoformulations were examined. A lung transplant-simulated cell culture model was used to evaluate therapeutic efficacy in vitro. A pulmonary ischemia-reperfusion (IR) model was used to test therapeutic efficacy in vivo. GNP-Peptide hybrids showed good stability with high cellular uptake. GNP-PKCi formulations demonstrated anti-inflammatory and anti-apoptotic effects in vitro. When administered to rats under IR stress, GNP-PKCi formulation improved blood oxygenation, reduced pulmonary edema and histological lung injury. In conclusion, we have successfully formulated a clinically-applicable nanoparticle with therapeutic potential to ameliorate lung injury and inflammation. Our formulation strategy could be used to deliver other peptide-based drugs.
Multidisciplinary Design Optimization of a Morphing Wingtip Concept with Multiple Morphing Stages at Cruise
Keywords: Optimization
Morphing Aircraft
Particle Swarm
Multidisciplinary

Morphing an aircraft wingtip can provide substantial performance improvement. Most civil transport aircraft are optimized for range but for other flight conditions such as take-off and climb they are used as constraints. These constraints could potentially reduce the performance of an aircraft at cruise. By altering the shape of the wingtip, we can force the load distribution to adapt to the required flight condition to improve performance. Using a Variable Geometry Truss Mechanism (VGTM) concept to morph the wingtip of an aircraft with a Multidisciplinary Design Optimization (MDO) framework, the current work will attempt to find an optimal wing and wingtip shape to minimize fuel consumption for multiple morphing stages during cruise. This optimization routine was conducted with a Particle Swarm Optimization (PSO) algorithm using different fidelity tools to analyze the aerodynamic and structural disciplines.
Validation of the Magneto-articulography for the Assessment of Speech Kinematics (MASK) System and Testing for Use in a Clinical Research Setting
Keywords: articulography
speech
MEG
position tracking
error mapping
electromagnetic
speech kinematics
error testing

A novel technology, the Magneto-articulography for the Assessment of Speech Kinematics (MASK) system, which measures brain activity and oromotor movement simultaneously, was validated for its speech tracking capabilities. MASK has not been systematically tested, so its movement tracking accuracy and practicality for research was still unknown. An error testing and mapping protocol is developed to validate MASK accuracy against established electromagnetic articulography (EMA) speech tracking systems. Data from human speech experiments are also compared. MASK exhibited higher positional error and fluctuation than EMA, and more inconsistent distribution of errors. Error mapping and potential error correction protocols were also developed. MASK spatial and temporal resolutions were found insufficient for precise tracking of small and quick articulatory movements. MASK requires much improvement to reach the capabilities of EMA. Further investigation into numerical instabilities of the position calculation algorithms is encouraged. This project provides the first assessment of MASK, which may advance speech research for future applications.
Octaarginine Labelled 30 nm Gold Nanoparticles as Agents for Enhanced Radiotherapy
Keywords: gold nanoparticle
radiotherapy

Traditional radiation therapy is limited by the radiotoxic effects on surrounding healthy tissues. This project investigated the use of a gold nanoparticle (AuNP) conjugated to a cell-penetrating peptide (CPP) to increase tumour cell death during radiotherapy by maximizing the cellular import of the gold nanoparticles. ~8300 octaarginine CPPs were coupled per 30 nm AuNP through poly(ethylene glycol) spacers (AuNP-PEG-CPP). The CPPs enhanced the internalization of the AuNPs into three human breast cancer cell lines by a factor &gt;2 as compared to untargeted AuNPs. Cells were treated with AuNP-PEG-CPP for 24 hours, prior to radiotherapy and their long-term proliferation was assessed in clonogenic assays. The increased internalization of AuNPs by the CPPs resulted in greater cell death following exposure to 300 kVp radiotherapy, by a dose enhancement factors between 1.3 and 2.1 depending on the cell line. These findings illustrate the potential of using AuNP-CPPs to enhance radiotherapy in patients.
Detecting Cognitive Dysfunction in Multiple Sclerosis: Assessing the Validity of a Computer Generated Battery
Keywords: multiple sclerosis
cognition
neuropsychology
computerized cognitive assessment

Approximately half of Multiple Sclerosis (MS) patients experience cognitive deficits. Accessing neuropsychological assessment can be challenging due to the considerable time, expense, and expertise required for test administration. Computerized cognitive testing has been proposed as an alternative. The objective was to validate a computer generated cognitive screen for MS patients. Ninety-nine MS patients and 98 healthy controls completed the computerized battery consisting of the Stroop, Symbol Digit Modalities Test (C-SDMT), Paced Auditory Serial Addition Test (PVSAT-2, PVSAT-4), and simple and choice reaction time tests. The Minimal Assessment of Cognitive Function in MS (MACFIMS) was used to define cognitive impairment in the MS sample. A combination of the C-SDMT, PVSAT-2, PVSAT-4 had a sensitivity of 83.3% and specificity of 87.7% in detecting cognitive impairment. Each measure had good test-retest reliability (p < 0.001). High sensitivity and specificity, and brevity emphasize the usefulness of the computerized cognitive screen in busy MS clinics.
The Kwakwaka’wakw Potlatch Collection and its Many Social Contexts: Constructing a Collection’s Object Biography
Keywords: Object Biography
Museum Collections
Kwakwaka'wakw
First Nations
repatriation
potlatch collection
objecthood
subjecthood
institutional forgetting
cultural centres

In 1921, the Canadian government confiscated over 400 pieces of Kwakwaka’wakw potlatch regalia and placed it in three large museums. In 1967 the Kwakwaka'wakw initiated a long process of repatriation resulting in the majority of the collection returning to two Kwakwaka’wakw cultural centres over the last four decades. Through the theoretical framework of object biography and using the museum register as a tool to reconstruct the lives of the potlatch regalia, this thesis explores the multiple paths, diversions and oscillations between objecthood and subjecthood that the collection has undergone. This thesis constructs an exhibition history for the regalia, examines processes of institutional forgetting, and adds multiple layers of meaning to the collection's biography by attending to the post-repatriation life of the objects. By revisiting this pivotal Canadian case, diversions are emphasized as important moments in the creation of subjecthood and objecthood for museum objects.
Exploring the Role of Hypoxia-related Parameters in the Vascularization of Modular Tissues
Keywords: Tissue engineering
Hypoxia
Vascularization
Mesenchymal stromal cells
Endothelial cells

Modular tissue engineering involves assembling tissue constructs with integral vasculature from units containing adipose-derived mesenchymal stromal cells (adMSCs) and endothelial cells. Here, the effects of implant volume and adMSC density on the vascularization of modular tissues were explored. Both parameters affected the contributions of host- and graft-derived vessels, without affecting total vessel density. Increasing implant volume from 0.01 to 0.10 mL increased HIF1&alpha; expression and graft-derived vessel density, suggesting a role of hypoxia in graft-derived vessel formation. However, increasing adMSC density within small-volume implants did not increase HIF1&alpha; expression. Vascularization of small-volume implants of high (4.3&bull;10^6 cells/mL) and low (1.0&bull;10^6 cells/mL) adMSC densities was dominated by host vessel ingrowth at day 7. By increasing adMSC density, a high proportion of host-derived vessels was maintained to day 14, presumably via paracrine effects. Further dissection of the role of hypoxia in modular tissue engineering remains a promising avenue to pursue.
Somatic Copy Number Aberrations in Familial Pancreatic Cancer: Integrative Genomics and Gene Discovery
Keywords: Cancer
Pancreatic
CNV
Genomics
Exome
Sequencing

Familial Pancreatic Cancer (FPC) is an autosomal dominant condition with greater then 80% of genetic causes unknown. We hypothesize that an integrative approach employing germline exome sequencing and somatic microarray analysis of FFPE DNA will identify novel tumour suppressor genes (TSGs). 55 FPC and 21 sporadic PDAC tumours were analyzed on the Affymetrix Oncoscan FFPE Express 2.0 SNP microarray and compared to data from 33 germline FPC cases analyzed on the Illumina GAIIx Analyzer. We have demonstrated that FPC is genetically heterogeneous with recurrent loss at CDKN2A/p16, TP53 and SMAD4. Analysis of 2 sisters has shown a shared loss region involving DCLK3 and SERPINF1. By an integrative approach, we have identified ATPAF1-AS1 and MAP3K6 as potential TSGs. Germline variants of these genes have been confirmed by Sanger sequencing and somatic fluorescence in-situ hybridization. Future functional studies will better characterize the importance of these regions and novel putative TSGs in FPC.
Investigating Perception Under Dynamic Auditory Conditions in the Acoustic Parasitoid Fly Ormia ochracea
Keywords: Neuroethology
Behaviour
Psychophysics
Non-associative Learning

Behavioural phonotaxis (oriented movement in response to sound) is an effective means to quantify auditory perception in acoustically communicating insects. Previous phonotaxis studies on the acoustic parasitoid fly Ormia ochracea (Diptera: Tachinidae) have described stereotyped, reflex-like responses towards auditory stimuli modeled after their preferred cricket hosts, yet their ability to demonstrate plasticity of responses in the context of dynamically changing auditory cues has not previously been described. Using a behavioural sensitization protocol, I compared phonotaxis towards behaviourally irrelevant (non-attractive) test stimuli presented alone, and when preceded with the natural, response-evoking cricket song (attractive). Results demonstrate the cricket song as a sensitizing stimulus mediating phonotaxis towards otherwise non-attractive sounds, and differential walking patterns depending on temporal delay between song offset and test stimulus onset. My findings suggest an ecological purpose of sensitization, allowing flies to maintain orientation towards a cricket host amidst conditions of signal disruption in the environment.
Advances in Fault Diagnosis and Fault Tolerant Control Motivated by Large Flexible Space Structure
Keywords: Fault Diagnosis
Fault Tolerant Control
Large Flexible Space Structure
Control

In this thesis, two problems are studied. The first problem is to find a technique to generate a particular type of failure information in real time for large flexible space structures (LFSSs). This problem is solved by using structured residuals. The failure information is then incorporated into an existing fault tolerant control scheme. The second problem is a ``spin-off'' from the first. Although the H-infinity sliding mode observer (SMO) cannot be applied to the colocated LFSS , its ability to do robust state and fault estimation of the SMO makes it suitable to be used in an integrated fault tolerant control (IFTC) scheme. We propose to combine the H-infinity SMO with a linear fault accommodation controller. Our IFTC scheme is closed loop stable, suppresses the effects of faults and enjoys enhanced robustness to disturbances. The effectiveness of the IFTC is illustrated through the control of a permanent magnet synchronous motor under actuator fault.
Extinction Limits of Laminar Diffusion Counterflow Flames of Various Gaseous Fuels including Syngas and Biogas
Keywords: Combustion
Strain Rate
Extinction
Counterflow
Soot
Flame
Hydrogen
Biofuels
Syngas
Biogas
Diffusion

This work investigates the extinction limits of laminar diffusion counterflow flames for various gaseous (methane, syngas, biogas) fuels using a high flow rate counterflow burner designed and built for this work. Equal momenta of the fuel and oxidizer streams were not maintained to provide data to check the fidelity of the numerical schemes and their chemical mechanisms at "non-standard" conditions. Strain rate values at extinction were obtained as a function of fuel mole fraction. Preliminary work with the new burner found that the methane extinction limit results were consistent with results from literature. The results provide insight into the extinction limit conditions of the aforementioned fuels. The strain rate was found to increase with increasing fuel mole fraction. Extinction limit results indicated that fuels with the highest concentration of hydrogen have the greatest extinction limit, which is believed to be attributed to the high diffusivity and reactivity of hydrogen.
Towards Longitudinal Control for Over-the-horizon Autonomous Convoying
Keywords: Convoy
Longitudinal control
Autonomous vehicles

In a variety of military operations, a convoy of autonomous followers may need to traverse the leader's path without using Global Positioning System (GPS), lane markers/magnets and/or a vision-based vehicle-following system. This can be achieved by using Visual Teach and Repeat (VT and R), which provides an effective method for autonomous repeating of a previously driven path. This thesis describes the design of a distributed control system that uses the idea behind the VT and R method to allow a convoy of inter-communicable autonomous vehicles to follow a manually-driven lead vehicle's path with a desired inter-vehicle spacing, even when the leader is not in the camera view of the followers. The longitudinal controller is designed for addressing a 1D spacing problem and then combined with a path tracker for tracking a path in a 2D environment. The designed control model is tested in simulations.
Novel Metallic Field-effect Transistors
Keywords: metallic
transistor
gold
nanoscale
simulation
density of states

This thesis describes a novel concept for a field-effect transistor based on metallic channels. Latest research demonstrates that the bulk (3D) properties of many materials begin to change when confined to 2D sheets, or 1D nanowires. Particularly, the bandgap increases and the density of states decreases. In this work, this effect is explored further to demonstrate its application to field-effect transistors. Certain metals such as Gold and Silver in these dimensions have extremely low density of states in particular energy regions and through gate modulation can be partially depleted from electrons thus creating conditions for field-effect. A simulation study of Gold channel FET demonstrates ION/IOFF of 30 and superior current driving capability compared to the state-of-the art 22nm SiGe ETSOI as well as 30nm nanotube transistors.