VictorJuiz/thesis huggingface dataset:
Designing the Next-generation Oncolytic Vaccinia Virus
Keywords: Cancer therapy
Interferon
Oncolytic virotherapy
Peritoneal Carcinomatosis
Vaccinia Virus
vvDD

Many oncolytic viruses (OVs), such as double-deleted vaccina virus (vvDD), are engineered with enhanced tumor-selectivity based on increased cell proliferation in cancer cells. We proposed that OVs with improved tumor efficacy and equal tumor-selectivity could be generated by exploiting the dysregulated immune response in tumors. Vaccinia virus (VV) proteins that inhibit the interferon response are redundant for replication in tumors, which often already have a decreased interferon response. We deleted VV immunomodulatory genes (N1L, K1L, K3L, A46R, or A52R) from VV and compared these candidate VVs to vvDD. Candidate VVs demonstrated equal or superior in vitro viral replication, spread, and tumor cytotoxicity in colon cancer cells compared to vvDD and were potent against ovarian cancer cells. At doses 20-1000 times less than the vvDD treatment dose, the best in vitro candidate VVs (â K1L, â A46R, â A52R VVs) demonstrated tumor-selectivity and equal or prolonged survival in mouse models of peritoneal carcinomatosis.
Classification of Pre-clinical Seizure State Transitions in Scalp EEG using Global Cross-frequency Coupling Index
Keywords: Cross Frequency Coupling
EEG
Epilepsy
Seizure Detection

In 30% of individuals that suffer from epilepsy, seizures remain uncontrolled by drug therapy. The unpredictability of clinical seizures reduces patient quality of life, ability to function in society, and increases their risk of SUDEP. This work aims to improve the state of the art of pre-clinical seizure detection systems so that they can be implemented to monitor patients, particularly, in the home environments outside the clinic. Simultaneous intracranial and scalp EEG recordings from patients with drug resistant epilepsy were used to examine cross-frequency coupling (CFC) features as a marker for the detection of a pre-clinical seizure state transition. Machine learning based classifiers were trained and combined in an expert system to identify pre-clinical seizure state transitions in a multi-patient, multi-seizure data set. This work shows that CFC features could be implemented in a home monitoring system to give advanced warning to patients and caregivers of an upcoming clinical seizure.
Fracture Strength of Implant-supported Full-contoured Titanium and Zirconia Single Crowns Connected to Titanium Cores
Keywords: Artificial aging
Customized crown
Dental implant
Fracture strength
Titanium insert
Zirconia

Objectives: To investigate the fracture strength and failure mode of implant-supported screw-retained customized 2-piece zirconia and 1-piece titanium restorations, and to evaluate the effect of aging on the mechanical performance of zirconia restorations. Materials and Methods: Thirty identical specimens simulating maxillary first premolar replacements were divided in 3 groups. Groups ZrA and ZrNA consisted of zirconia and Group Ti consisted of titanium restorations, anchored to implants embedded in PMMA. Specimens in Group ZrA underwent chewing simulation. Static load was applied until failure. Results: Group Ti showed the highest fracture strength. The difference was significant between Groups ZrA and Ti. Failures included partial or complete fracture of titanium insert or deformation of restoration with screw fracture. Conclusion: Evidence was inadequate to reject similarity in fracture strength between non-aged zirconia and titanium restorations, or between zirconia restorations with different aging conditions. Aging affected the failure mode of zirconia restorations.
Development of a Multiplexed Panel Assay for the Rapid Detection of Bacterial Resistance to β-Lactam Antibiotics using Liquid Chromatography – Tandem Mass Spectrometry
Keywords: antibiotic resistance
antibiotic susceptibility testing
beta-lactamase enzyme
gram-negative bacteria
multiplexed panel rapid assay
tandem mass spectrometry

Antibiotic susceptibility testing (AST) can involve automated platforms that produce results in 10 hours following bacterial colony growth. However, the total time can vary between 10-72 hours before definitive treatment can begin. An assay was developed for the detection of bacterial resistance conferred by enzymatic degradation of β-lactam antibiotics with the goal of designing a liquid chromatography – tandem mass spectrometry method capable of performing AST at an accelerated rate. The assay consisted of a one-hour bacterial incubation with a multiplexed panel of ampicillin, cefazolin, cefotaxime, and imipenem at 0.5 μg/mL, and a concurrent incubation of cefoxitin at 2 μg/mL. The assay used the extent of antibiotic hydrolysis as a means of measuring resistance quantitatively. Hydrolysis percentages were obtained by chromatographic peak area integration. The assay was able to differentiate carbapenemases, Class A β-lactamases, and AmpC β-lactamases. A resistance profile could be obtained in 2 hours, 35 minutes following colony growth.
Carbon Sequestration Strategies in Cement Based Material: Carbon Nano Platelet Admixture Interaction and Long term Carbonation of CO2 Injected Concrete Blocks
Keywords: adsorption
air entrainment
carbonation curing
carbon nano platelet
carbon sequestration

Two novel approaches to sequester carbon in concrete were examined in this study. First, carbon nano platelets exposed to CO2-laden flue gas were explored for possible use as a concrete additive to improve mechanical properties. However, carbon nano platelets also have the potential to interfere with the performance of air entraining admixtures (AEAs) in concrete. The capacity for carbon to adsorb AEAs is already widely recognized in terms of unburnt carbon residues present in coal combustion fly ash. In this research, adjustments to Vinsol resin and synthetic AEA dosages necessary to maintain adequate air void parameters in mortars were determined using a combined adsorption isotherm test based on chemical oxygen demand (COD). Second, the long-term carbonation of industrially produced concrete blocks manufactured using early-age CO2 injection was explored using an accelerated carbonation chamber. Carbonation rates were found to be similar for CO2-injected and non CO2-injected blocks.
Characterizing the Contribution of First and Second Heart Field-derived Cells in Zebrafish Cardiac Development
Keywords: Cardiac Development
Developmental Biology
Second Heart Field

Vertebrate heart development occurs through contribution from two spatio-temporally distinct progenitor populations termed the First Heart Field (FHF) and Second Heart Field (SHF). In the mammalian heart, the FHF gives rise to the left ventricle and parts of both atria, whereas the SHF contributes to the right ventricle, inflow and outflow tracts, and portions of the atria. Here I employed a cmlc2 driven CreERT and switch reporter lines to lineage trace the two populations in the adult zebrafish heart. Late differentiating cells, as displayed through EGFP-positive cells consistently made a significant contribution to the cortical layer of the adult heart, which has been shown to be a major source of new cardiomyocytes following cardiac injury. Cells derived from the proposed SHF population give rise to the primordial layer, as well as the trabeculae in the ventricular base. The cortical and primordial layers are partially derived from the SHF progenitor population.
Genetic Counsellors' Preferences for Preimplantation Genetic Diagnosis: A Discrete Choice Experiment
Keywords: Discrete Choice Experiment
Genetic Counsellors
Health Policy
Preimplantation Genetic Diagnosis
Public Coverage

Preimplantation genetic diagnosis (PGD) is a way of testing for a genetically affected embryo. Provincial PGD coverage differences along with ambiguity around scope of testing and patient inclusion criteria create a lack of clarity for public coverage options. A discrete choice experiment was undertaken with Canadian genetic counsellors (GC) to quantify their stated preferences for public PGD coverage, considering the following attributes: PGD indication, risk of the condition, fertility status, family history and number of cycles covered. The completed response rate was 41% with 126 GC completing the survey. Multinomial logit regression was used to estimate part-worth utilities. Key demographic and practice characteristics were considered as preference influences. Risk of the condition was the most important attribute. Overall, GC preferred scope of testing criteria over patient inclusion criteria. This is the first study to quantify GC preferences for PGD coverage and provides insight to help promote discussion about PGD policy.
Exploring DNA Methylation in Tumour-adjacent Normal Prostate Tissue and Evaluating its Role as a Biomarker for PCa Detection
Keywords: Biomarkers
Biopsy
Diagnosis
DNA Methylation
Field Cancerization
Prostate Cancer

DNA methylation alterations as a result of field cancerization may be used as diagnostic biomarkers to improve Prostate Cancer (PCa) detection. To identify diagnostic biomarkers, we evaluated DNA methylation of KRTAP27-1, APC, HOXD3, CRIP3, KLK6 and RASSF1A in tumour, tumour-adjacent normal (TAN) and benign prostate tissue. DNA methylation of APC, RASSF1A and GSTP1 was detected in TAN tissue up to 8 mm from the tumour. KRTAP27-1 was discovered to be hypermethylated in TAN tissue using Global DNA methylation profiling. Overall methylation concordance of all genes between matched radical prostatectomy (RP) tumour and RP TAN or biopsy (Bx) TAN tissue was 81% and 66%, respectively. Hypermethylation of RASSF1A, KRTAP27-1 and HOXD3 in combination were most significantly associated with PCa (Benign vs. RP TAN: p = 5.87 x 10^-10, Benign vs. Bx TAN cases: p = 4.44 x 10^-8). My project demonstrates the benefit of using field cancerization biomarkers for PCa diagnosis.
Game Design for Stroke Rehabilitation Robots: A Pilot Study Comparing Masked Versus Unmasked Game Designs
Keywords: Gamification
Masking
Motivation
Rehabilitation robotics
Stroke

Appropriately-designed computer games can improve rehabilitation therapy outcomes by motivating stroke survivors to follow through with exercises. Supplementing conventional therapy with computer games and robotics enables patients to continue without therapists constantly present for repetitive parts of therapy. Studies have used “Basic” (framed as target exercise), “Unmasked” (simulating everyday activity), or “Masked” (fantasy activity) games, without addressing which design best maintains stroke survivors’ motivation and time on task. Three such games were developed for an upper limb robot and analyzed with gameplay measurements, questionnaires, and observations determining which game users preferred, played longer, and performed more repetitions. The “Masked” game had the greatest preference “votes” (5), time on task (24.2 ± 11.6 minutes), and motion repetitions (1191 ± 778), but also misses (180 ± 211) and standard deviations. We should individually tailor games, but continue developing “Masked” games, possibly blending game types. Future design and process recommendations were listed.
Aerodynamic Shape Optimization of a Box-wing Regional Aircraft Based on the Reynolds-averaged Navier-Stokes Equations
Keywords: Aerodynamic Shape Optimization
Box Wing
Computational Fluid Dynamics
High Fidelity
Sustainable Aviation
Unconventional Aircraft Configurations

The box wing is an unconventional aircraft configuration that has the potential to provide major savings in fuel consumption relative to the conventional cantilever wing. In order to further develop and evaluate this potential, high-fidelity aerodynamic shape optimization is applied to the aerodynamic design of a box wing and a cantilever wing, based on the Embraer E190 regional jet, with the latter serving as a performance baseline. The optimization framework consists of B-spline parameterization, free-form and axial deformation geometry control, an integrated mesh-movement scheme based on the theory of linear elasticity, a Newton-Krylov-Schur flow solver for the Reynolds-averaged Navier-Stokes equations, a gradient-based optimizer, and the discrete-adjoint method for gradient evaluation. Results indicate that a box-wing with a height-to-span ratio of 0.26 burns 7.61% less fuel at cruise than a conventional baseline of the same span and lift. Aerodynamic trends and trade-offs are investigated, and a weight sensitivity study is performed.
Microfluidic Investigations of CO2 and H2 Activation by Lewis Pairs
Keywords: Frustrated Lewis Pairs
Lewis Acids
Lewis Bases
microfluidics
microreactors
thermodynamics

A microfluidic strategy has been used for the time- and labour-efficient evaluation of the relative efficiency and thermodynamic parameters of CO2 binding by three Lewis acid/base combinations, where efficiency is based on the amount of CO2 taken up per binding unit in solution. Neither tBu3P nor B(C6F5)3 were independently effective at CO2 capture, and the combination of the imidazolin-2-ylidenamino-substituted phosphine (NIiPr)3P and B(C6F5)3 was equally ineffective. Nonetheless, an archetypal frustrated Lewis pair (FLP) comprised of tBu3P and B(C6F5)3 was shown to bind CO2 more efficiently than either the FLP derived from 2,2,6,6-tetramethylpiperidine (TMP) and B(C6F5)3 or the highly basic phosphine (NIiPr)3P. Moreover, the proposed microfluidic platform was used to elucidate the thermodynamic parameters for these reactions. This microfluidic approach was also applied to obtain thermodynamic parameters for H2 activation by the FLP comprised of tBu3P and B(C6F5)3 with subsequent kinetic studies underway.
Progress Towards the Total Synthesis of Depsipeptide Natural Products: Teixobactin and the Xentrivalpeptide Family
Keywords: Chemistry
Depsipeptides
Organic
Synthesis
Teixobactin
Xentrivalpeptides

Depsipeptides (cyclic peptides containing one or more ester bond within the ring) are a class of natural products, many of which display biological activity, including antimicrobial and anticancer compounds. Depsipeptide synthesis via macrolactonization is often plagued with low yields or failure to cyclize, and has remained a challenge compared to lactamization. Despite this, macrolactonization of the seco-acid is still a preferred method due to facile synthesis of the linear precursors using solid-phase peptide synthesis (SPPS). The Batey group has recently published an efficient method of macrolactonization using lanthanide-(III) triflate salts alongside MNBA (Shiinaâ s reagent) for rings containing five amino acids. This method has been extended to include rings of various sizes. In particular, cyclizations of model systems towards the core of teixobactin, and the total synthesis of xentrivalpeptide A, Q and related analogues are reported.
The influence of the presence of a dog or cat on perceptions of a psychotherapist
Keywords: animal-assisted interventions
human-animal interaction
psychotherapy
therapeutic relationship

This experimental study examined the effects of companion animal presence on perceptions of an observed psychotherapist. One hundred thirty-three adults (72.2% female; Mage = 38.05 years) participated in an online study which used randomly assigned visual vignettes to elicit responses to a psychotherapist. The vignettes are described as the following: psychotherapist with a dog; with a cat; client touching dog; touching cat, and; no animal present. Respondents evaluated the therapist on various characteristics, and indicated willingness to self-disclose. Overall, participants rated the therapist as more friendly and likable when shown with an animal than without, but self-disclosure was not influenced by animal presence. There was no differential impact of animal type on the outcome measures. Implications for psychotherapy and methodological challenges of the study are discussed.
Acoustic and Strobe-light Behavioural Barriers: Examining Behavioural and Movement Responses of Common Carp (Cyprinus carpio) at Laboratory and Mesocosm Scales
Keywords: acoustic telemetry
Asian carp
behavioural barrier
invasive species
mesocosm

Acoustic and strobe-light behavioral barriers have been recognized as tools to limit the spread of Asian carps in the Great Lakes. Urgent research is needed to understand how these stimuli impact behaviour, and to evaluate barrier efficacy within realistic canal environments. In a laboratory study, Common Carp responses to stimuli were recorded with video trials (n=44). There were no differences in behavioural responses to acoustic, strobe-light, or combined stimuli. The stimulus period increased durations of carp movement, and the post-stimulus period had increases in movement duration and barrier passes. In a mesocosm study, Common Carp (n=6) and buffalo (n=3) were exposed to the same stimuli, and movement was analyzed using acoustic telemetry. Acoustic stimuli did not produce significant movement responses. Strobe lights (n=12) produced smaller utilization distributions, a decrease in relocations, and an increase in travel velocity near the stimuli (
Math Discourse in a Grade 2 Knowledge Building Classroom
Keywords: Geometry
Knowledge Building
Math Talk
Online Discourse

The goal of this study was to examine grade two Math Talk in geometry within a Knowledge Building community engaged in both face-to-face and computer-mediated discourse. Ontario Ministry of Education guidelines were used to identify grade two geometry concepts. Math vocabulary extracted from these guidelines was used, along with a content-based social network analysis tool, to explore the emergence of new domain-specific vocabulary in student discourse and to assess patterns of engagement surrounding use of those terms. A â Ways of Contributingâ analytic framework was used to assess the nature of both teacher and student contributions to face to face and online discourse. Findings suggest that students as early as grade 2 can engage productively in Knowledge Building Math Talk in both face-to-face and online contexts.
A Powered Wheelchair Parking Assistance Reasoning Co-pilot (PARC) System for Cognitively Impaired Older Adults
Keywords: Assistive Technology
Docking
Human-Robot Interaction
Intelligent Wheelchairs
Shared Control
Usability

Intelligent Powered Wheelchairs (IPWC) can help maintain the independence of older adults with cognitive impairment who are unsafe powered wheelchair drivers. Docking at tables is a challenging task unaddressed by IPWCs. Following a requirements analysis, the Parking Assistance Reasoning Co-pilot (PARC) was designed to provide collision-free semi-autonomous docking assistance. Twenty adults docked a PWC with and without PARC under various conditions. PARCâ s docking success rate was 90.4%. Compared to the control group, PARC intervention reduced table collisions, had no effect on user satisfaction, other obstacle collisions, and perceived workload, but reduced other usability measures. A case study of two older adult powered wheelchair drivers yielded similar findings with contrasting acceptance and need of PARC between participants. In both studies, table collisions were frequent in control conditions. Skilled driers would benefit from PARCâ s table collision avoidance without navigation assistance. Further investigation into the determinants of IPWC acceptance and usability is recommended.
Multi-network Analysis of Kindergarten Children's Interactions as a Foundation for Drosophila melanogaster Interaction Networks
Keywords: Hierarchy
Kindergarten Children
Layered Networks
Social Behaviour
Social Structure

Group structure is important for social animals like humans, where who we interact with can influence both our happiness, and our health. One of the ways we can examine a group’s organizational structure is through social network analysis. Traditionally, networks have only been extracted and examined for a single type of interaction between individuals (e.g. friendship, smoking, happiness). Yet we know that most animals, including humans, interact in multiple ways, and these different interactions and their targets may be related. Here, I take an unbiased multi-network approach to adapt existing methods into a protocol to investigate relationships between interaction types and their contributions to group structure. Application of this method to a dataset of kindergarten children’s interactions reveals non-trivial underlying patterns in children’s classroom social structures. Potential applications of this protocol to other social groups, particularly Drosophila, are discussed.
Characterizing Acquired Proteasome Inhibitor Resistance in Human Multiple Myeloma Cell Lines
Keywords: drug resistance
multiple myeloma
mycoplasma
proteasome inhibitor

Proteasome inhibitors (PIs) are a mainstay treatment for multiple myeloma (MM). Unfortunately, cure is rare. Here, we attempted to define mechanisms for PI resistance. Two PIresistant MM cell lines were serendipitously developed by blasticidin exposure. These cells had unfolded protein response profiles resembling their PI-sensitive parental cell lines. PI resistance was demonstrated to be due to Mycoplasma infection, which impeded drug inhibition of the proteasome target. Screening of patient samples however did not reveal mycoplasma infection in primary MM cells. Instead, gene expression analyses of primary MM suggested that epigenetic dysregulation (revealed by cancer testis antigen expression) correlates with clinical bortezomib resistance. We therefore screened small molecule epigenetic probes to identify regulators of PI response. While most had no effect on PI response, MM inhibition and bortezomib sensitization was observed with the pan-BET inhibition, JQ1, suggesting that additional evaluation of PIs in combination with BET (or BRD4) inhibitors is warranted.
Differential Regulation of IgA+ B Cells in Vitro by Stromal Cells from Distinctive Anatomical Compartments
Keywords: B cells
gut
IgA cells
plasma cells
stromal cells

B cell development is regulated by stromal cells that form a supportive microenvironment. Bone marrow (BM), spleen (Sp), and the gut lamina propria (LP) constitute distinct anatomical compartments that support B cell differentiation. In order to examine the effect of stromal cells on IgA+ B cells, I developed an in vitro system to co-culture gut LP, BM, or Sp-derived stromal cells with B cell progenitors to characterize the signals to generate IgA+ B cells. In this study, I characterized optimal conditions for the in vitro generation of IgA+ B cells. I found that gut LP stromal cells promote IgA+ B cell accumulation through producing soluble stimulatory factors. In contrast, BM and Sp stromal cells impaired IgA+ B cell accumulation in vitro by inhibiting proliferation and differentiation of IgA+ B cells. These observations provide new insights into how stromal cells from different anatomical locations shape IgA+ B cell responses.