VictorJuiz/thesis huggingface dataset:
Quantitative and Depth-resolved Fluorescence Guidance for the Resection of Glioma

The clinical management of glioma remains a challenge. The prognosis is poor—for glioblastoma multiforme, the most virulent of these brain cancers, survival is only ~1 year. Surgical resection of the tumor is the first line of defense. Several studies demonstrate a survival advantage in patients who undergo near-complete tumor resection; however, achieving complete resection is limited by the difficulty of visualizing residual tumor after de-bulking. Intraoperative fluorescence guidance is a promising candidate to better visualize residual tumor. The most clinically developed form uses protoporphyrin IX fluorescence, the precursor to heme in its biosynthesis which preferentially accumulates in tumor cells after the administration of 5-aminolevulinic acid. Challenges remain in quantitatively assessing the fluorescence to reduce variability of outcome and improve tumor detection specificity, and in observing sub-surface tumor fluorescence. To these ends, this work outlines the development of intraoperative techniques to 1) quantify tissue fluorescence using a handheld fiberoptic probe and 2) improve detection by reconstructing the depth-resolved fluorescence topography of sub-surface tumor. As a critical component to achieve these objectives, a technique to measure the tissue optical properties was developed. This technique used diffuse reflectance measurements mediated by a handheld fiberoptic probe to derive the tissue optical properties. The handheld fiberoptic probe was further developed to include fluorescence spectroscopy. A novel algorithm to combine the fluorescence measurement and the tissue optical properties was derived in order to extract the quantitative fluorescence spectrum, i.e. fluorescence without confounding effects of tissue optical properties. The concentration of fluorescent tumor biomarker can then be extracted. The quantitative fluorescence work culminated in deployment of the fiberoptic probe in clinical trials for the resection of intracranial tumors. The quantitative fluorescence probe out-performed a state-of-the-art fluorescence surgical microscope for a broad range of brain tumor pathologies. A novel technique for depth-resolved fluorescence detection was developed utilizing multi-excitation fluorescence imaging. An algorithm to extract depth information from the multi-excitation images was derived, with validation in phantoms and a rat brain tumor model. This demonstrates the potential for depth-resolved fluorescence imaging, which there is a clear need for in tumor resection guidance.

Keywords: fluorescence
tissue optics
neurosurgery
cancer diagnostics
tumor detection
optical spectroscopy
Advisor: Wilson, Brian Campbell
Structural Characterization of the anti-HIV-1 Broadly Neutralizing Monoclonal Antibody 2F5

Human immunodeficiency virus type 1 (HIV-1), the pathogen responsible for the onset of acquired immuno-deficiency syndrome (AIDS) in humans has reached pandemic proportions. To this day, no cure is available for infection with this virus and the only treatment option for this chronic infection is the life-long adherence to anti-retroviral therapy. Efforts in the quest to control the worldwide AIDS pandemic include the search for an effective anti-HIV-1 vaccine. Providing hope in this endeavor are a few monoclonal antibodies possessing broad neutralizing characteristics (bnmAbs) that have been isolated from the sera of rare patients that have a delayed progression to AIDS. In this thesis, one of these bnmAbs, 2F5 is extensively characterized at the atomic level to better understand its binding and neutralization mechanism. In total, 27 crystal structures of the 2F5 Fab’ in complex with various peptides representing its linear gp41 membrane proximal external region (MPER) epitope are presented. Furthermore, expression of the 2F5 Fab in a bacterial system allowed to design mutants of the 2F5 Fab and therefore investigate the implication of specific domains of 2F5 in mediating binding and neutralization. Atomic level characterization of this immune complex revealed a somewhat promiscuous recognition of 2F5 for its 664DKW666 epitope as long as the following characteristics were conserved: the aspartate’s negative charge, the hydrophobic alkyl-pi stacking arrangement between the beta-turn lysine and tryptophan, and the positive charge of the former. Moreover, it was demonstrated that 2F5 has an elongated and flexible complementary determining region 3 loop of the heavy chain (CDR H3), which is required for neutralization and is involved in secondary binding interactions other than to its core linear epitope. These contributions will significantly help in guiding the structure-based design of an HIV-1 vaccine looking to elicit 2F5-like antibody responses.

Keywords: HIV-1
X-ray crystallography
Advisor: Pai, Emil F.
Effect of Methanol on the Microbial Community Structure of Biofilters Treating Dimethyl Sulphide

Odour emissions resulting from reduced sulphur compounds in the kraft pulping industry are frequently found in dilute, high flowrate air streams that are costly to treat using incineration and thermal oxidation. Biofiltration, an air treatment method involving passing air through a packed bed of microorganisms, has emerged as a promising treatment strategy for these dilute waste gas streams. However, biodegradation of dimethyl sulphide (DMS) in biofilters is rather poor and is limiting the application of biofiltration to odour streams rich in DMS. Recently, our group has shown that co-treatment of DMS with methanol can increase DMS removal significantly. In this thesis, the effect of methanol on the microbiology of two biofilters treating DMS was explored. Microbial community analysis revealed that the addition of methanol led to a significant increase of up to an order of magnitude in the abundance of Hyphomicrobium spp. in a biofilter co-treating DMS and methanol compared to a biofilter treating DMS alone with no significant difference in the abundance of Thiobacillus spp. between the two biofilters. Further to the biofiltration experiments, the growth kinetics of Hyphomicrobium spp. and Thiobacillus spp. on DMS and methanol in an enrichment culture created from a biofilter co-treating DMS and methanol were studied. A specific growth rate of 0.099 h-1 and 0.11 h-1 was determined for Hyphomicrobium spp. and Thiobacillus spp., respectively, growing on DMS at pH 7, double the highest maximum specific growth rate for bacterial growth on DMS reported to date in the literature. As the pH decreased from pH 7 to pH 5, the specific growth rate of Hyphomicrobium spp. decreased significantly by 85% in the mixed culture while the specific growth rate of Thiobacillus spp. remained similar through the same pH shift. When methanol was used as a substrate, the specific growth rate of Hyphomicrobium spp. declined much less over the same pH range (up to 30%). These results suggest that addition of methanol to biofilters co-treating DMS and methanol can increase DMS removal rates by increasing the abundance of DMS-degrading Hyphomicrobium spp. at pH levels not conducive to high growth rates on DMS alone.

Keywords: Biofiltration
Dimethyl Sulphide
Advisor: Allen, D. Grant
Liss, Steven N.
Group Information Behavioural Norms and the Effective Use of a Collaborative Information System: A Case Study

This research investigated whether Group Information Behavioural Norms (GIBNs) are correlated with the effective use of a collaborative information system. Previous research seeking to conceptualize ‘social influence’ in technology adoption has not attempted to include GIBNs. The dependent variable, ‘Effective Use’, comprised two subjective Effectiveness Judgments and three objective Actual Use measures. A mediating variable, ‘Group Adoption’ (GA) of the information system, was conceived as a behavioural expression of group norms and hypothesized to correlate with both GIBNs and Effective Use. It was also hypothesized that GIBNs would have a stronger relationship with Effective Use than the widely used Technology Acceptance Model (TAM) dimensions of Perceived Usefulness and Perceived Ease of Use. A mixed-methods case study approach was used because measurement of stable norms in workplace groups was required. A medium-sized engineering firm was chosen, and the collaborative information system studied was Knowledge Forum (KF), an educational research tool that was implemented to promote the exchange of information. There were both expected and unexpected results. GIBNs outperformed the TAM in explaining all three Actual Use variables, although the TAM was the sole significant correlate for one Effectiveness Judgment variable. Information Sharing and Proactive Information Use had opposite correlations with Effective Use, suggesting the existence of distinct information ‘sharing’ and ‘proactive use’ group norms. In addition, the TAM and GIBNs seem to have complementary influences on Effective Use. GA was unexpectedly observed to have the strongest relationship with Effective Use, having a significant relationship with four of five Effective Use measures. GA was also observed to mediate the TAM but not GIBNs. The results of a case study cannot be extensively generalized. However, the findings are important in three ways. First, this research provides evidence that GIBNs and the TAM exert complementary influences on Effective Use, and that Effective Use is best explained by also including GA. Second, GA may represent a valuable ‘social influence’ extension to the TAM, as a behavioural expression of group norms for collaborative information systems. Finally, this study illustrates the importance of a multi-dimensional conceptualization of ‘Effective Use’ of an information system.

Keywords: TAM
Group Adoption
Collaborative Information System
Group Information Behaviour
Effective Use
Knowledge Forum
Information Orientation
Effectiveness Judgments
Advisor: Choo, Chun Wei
"Toronto Has No History!" Indigeneity, Settler Colonialism, and Historical Memory in Canada's Largest City

The Indigenous past is largely absent from settler representations of the history of the city of Toronto, Canada. Nineteenth and twentieth century historical chroniclers often downplayed the historic presence of the Mississaugas and their Indigenous predecessors by drawing on doctrines of terra nullius, ignoring the significance of the Toronto Purchase, and changing the city’s foundational story from the establishment of York in 1793 to the incorporation of the City of Toronto in 1834. These chroniclers usually assumed that “real Indians” and urban life were inimical. Often their representations implied that local Indigenous peoples had no significant history and thus the region had little or no history before the arrival of Europeans. Alternatively, narratives of ethical settler indigenization positioned the Indigenous past as the uncivilized starting point in a monological European theory of historical development. In many civic discourses, the city stood in for the nation as a symbol of its future, and national history stood in for the region’s local history. The national replaced ‘the Indigenous’ in an ideological process that peaked between the 1880s and the 1930s. Concurrently, the loyalist Six Nations were often represented as the only Indigenous people with ties to Torontonians, while the specific historical identity of the Mississaugas was erased. The role of both the government and local settlers in crowding the Mississaugas out of their lands on the Credit River was rationalized as a natural process, while Indigenous land claims, historical interpretations, and mnemonic forms were rarely accorded legitimacy by non-Indigenous city residents. After World War II, with new influxes of both Indigenous peoples and multicultural immigrants into the city, colonial narratives of Toronto history were increasingly challenged and replaced by multiple stories or narrative fragments. Indigenous residents created their own representations of Toronto as an Indigenous place with an Indigenous history; emphasizing continuous occupation and spiritual connections between place and ancestors. Today, contention among Indigenous groups over the fairness of the Mississauga land claim, epistemic differences between western and Indigenous conceptions of history, and ongoing settler disavowal of the impact of colonialism have precluded any simple or consensual narrative of Toronto’s past.

Keywords: history
Canada
Toronto
Indigenous
Aboriginal
Native peoples
urban history
colonialism
historical memory
Anishinaabe
Mississaugas
Indigeneity
Haudenosaunee
Credit River
oral history
historical consciousness
Advisor: Morgan, Cecilia
Inhibition of Gamma Oscillations in Healthy Subjects and Patients with Schizophrenia

The pathophysiology of psychiatric disorders such as schizophrenia is not fully understood due, in part, to the shortcomings of available neurophysiological techniques. Previous studies have shown that patients with schizophrenia have deficits in dorsolateral prefrontal cortex (DLPFC). In this regard, two major deficits were observed: impairments in gamma-aminobutyric-acid (GABA) neurotransmission and cortical gamma (30-50Hz) oscillations. Previous in vitro and animal studies have linked the modulation of gamma oscillations with GABAB receptor mediated inhibition. Objectives: The first objective was to examine the effect of GABAB receptor mediated inhibition on cortical oscillations in the motor cortex and DLPFC in healthy subjects by using the novel technique of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) and through the TMS paradigm long interval cortical inhibition (LICI), which has been associated with GABAB receptor mediated inhibition. Second, to evaluate the psychometric properties of this neurophysiological paradigm, the validity and reliability of EEG indices of LICI were examined. Finally, the effect of LICI on cortical oscillations was examined in the DLPFC and motor cortex of patients with schizophrenia compared to healthy subjects and patients with bipolar disorder. Hypothesis: It was predicted that EEG measures of LICI would show validity and reliability, and it was hypothesized that patients with schizophrenia would show deficits in inhibition of gamma oscillations in DLPFC compared to healthy subjects and patients with bipolar disorder. Results: The first experiment showed that in healthy subjects LICI inhibited gamma oscillations in the DLPFC but not in the motor cortex. The second experiment demonstrated the validity and reliability of EEG indices of LICI were confirmed in healthy subjects. Finally, patients with schizophrenia had a selective deficit in inhibition of gamma oscillations in the DLPFC which appeared to be independent of illness duration or antipsychotic medication, and it was not observed in bipolar disorder. Conclusions: TMS combined with EEG allows for measuring modulatory effect of LICI on cortical oscillations. Inhibition of gamma oscillations in the DLPFC may be an essential neurophysiological process that may be impaired in schizophrenia. Future studies should ascertain the potential of gamma inhibition deficit as a biological marker for this illness.

Keywords: TMS
EEG
Schizophrenia
GABA
Advisor: Daskalakis, Zafiris Jeff
Wong, Willy
The Control of the Locust Spermatheca

The coordination of reproductive events in female locusts involves the interaction between sensory cells, reflex loops, and central pattern generators. Neurochemicals have also been identified as being important for initiating and/or modulating the activities of reproductive tissues. The present thesis investigates the association of neurochemicals with the spermatheca and the neural control of the spermatheca via a central pattern generator (CPG) that is coordinated with other reproductive events. Crustacean cardioactive peptide (CCAP)-like immunoreactivity is present in the innervation to the spermatheca of adult locusts. CCAP enhances basal tonus, spontaneous and neurally-evoked contractions and may function as a neuromodulator/neurotransmitter at the locust spermatheca. No locustatachykinin (LomTK)-like immunoreactivity is present in the innervation to the spermatheca, or on the spermatheca itself, whereas allatostatin-like immunoreactivity is present. LomTK1 is a stimulator of spermathecal contractions, but allatostatin 1 does not lead to any changes in spermathecal contractions. It is likely that LomTK acts as a neurohormone on the spermatheca, while the role of allatostatin remains unknown. Tyramine-like immunoreactivity is present in the nerves that project to the spermatheca and throughout all of its regions. Quantification of tyramine revealed that there is more tyramine than octopamine present in the spermatheca, and that tyramine can be released from the spermatheca by electrical stimulation of the ventral ovipositor nerve (VON). Physiological assays reveal that both tyramine and octopamine increase spermathecal contractions. Tyramine may be a co-transmitter with octopamine at the locust spermatheca. There is likely a central pattern generator (CPG) that controls the spermathecal muscle activity, that is regulated by descending inhibition. Extracellular nerve and electromyographic recordings demonstrate that this CPG appears to be localized within the VIIth and VIIIth abdominal ganglia and is found to integrate with the CPG that regulates oviposition digging in locusts.

Keywords: locust
reproduction
spermatheca
central pattern generators
neurochemicals
Advisor: Lange, Angela
Social Capital and Inequality in Singapore

Written as three publishable papers, this dissertation examines the sources of several forms of social capital in Singapore, and the effects of social capital on occupational success. Using representative survey data from Singapore, these papers make several important theoretical contributions: The first paper examines how and why categorical forms of stratification such as gender and ethnicity tend to produce distinctive forms of network inequalities: for example, whereas Chinese (relative to Malays and Indians) tend to have greater access to well-educated, wealthy, Chinese and weak tie social capital (but not non-kin), men (relative to women) tend to have greater access to men, non-kin and weak ties (but not well-educated, wealthy and Chinese). The key to understanding such distinctive patterns of network inequalities (by gender and ethnicity) is to understand the distinctive ways in which gender and ethnic groups are distributed in routine organizations such as schools, paid work and voluntary associations. The second paper examines the significance of personal contacts in job searches, in the context of Singapore’s meritocratic system. I show that in certain sectors such as the state bureaucracy, social networking brings no distinct advantages as appointments are made exclusively on the basis of the credentials of the candidates. Thus, personal contacts are not always useful, especially in labour markets that rely heavily on the signalling role of academic credentials to match people to jobs. In contrast, personal contacts are more useful among less qualified job searches in the private sector. The third paper shows that while job contacts (i.e. ‘mobilized’ social capital) may not always pay off in meritocratic labour markets, ‘accessed’ social capital remains extremely important. The leveraging power of social capital in meritocratic markets is not the active mobilization of job contacts per se, but more subtly, the result of embedded social resources such as knowing many university graduates and wealthy people. Together, these papers illustrate how socio-structural factors such as meritocracy, gender and racialization form important predictors of the distribution, role and value of social capital in everyday life and labour markets.

Keywords: Social capital
Inequality
Labour markets
Singapore
Social networks
Advisor: Erickson, Bonnie
Delta-Sigma Modulators with Low Oversampling Ratios

This dissertation explores methods of reducing the oversampling ratio (OSR) of both delta-sigma modulators and incremental data converters. The first reduced-OSR architecture is the high-order cascaded delta-sigma modulator. These delta-sigma modulators are shown to reduce the in-band noise sufficiently at OSRs as low as 3 while providing power savings. The second low OSR architecture is the high-order cascaded incremental data converter which possesses signal-to-quantization noise ratio (SQNR) advantages over equivalent delta-sigma modulators at low OSRs. The final architecture is the time-interleaved incremental data converter where two designs are identified as potential methods of increasing the throughput of low OSR incremental data converters. A prototype chip is designed in 0.18um CMOS technology which can operate in three modes by simply changing the resetting clock phases. It can operate as an 8-stage pipeline analog-to-digital (A/D) converter, an 8th-order cascaded delta-sigma modulator, and an 8th-order cascaded incremental data converter with an OSR of 3.

Keywords: delta-sigma modulator
incremental data converter
low oversampling ratio
Advisor: Johns, David A.
Erythropoietin Signaling in Pancreatic Beta Cells in Homeostasis and in Models of Type 1 and Type 2 Diabetes

Diabetes mellitus is a complex disorder characterized by chronic hyperglycemia and vascular complications leading to significant morbidity and mortality. The common feature in all forms of diabetes is the insufficient functional β-cell mass to maintain euglycemia; therefore, the promotion of β-cell survival and growth is a fundamental goal for diabetes prevention and treatment. Evidence has suggested that erythropoietin (EPO) exerts cytoprotective effects on non-erythroid cells. However, the in vivo role of EPO on the pancreatic β cells has not been evaluated to date. We hypothesized that EPO would have direct cytoprotective effects on the pancreatic β cells and provide protection against experimental models of diabetes. In Chapter IV, we report that recombinant human erythropoietin (rHuEPO) administration provided protection against diabetes development in the streptozotocin (STZ)-induced and db/db mice, models of type 1 and type 2 diabetes, respectively, through anti-apoptotic, proliferative and angiogenic effects within the islets. Next, we show in Chapter V, using β cell-specific EPO-R and JAK2 knockout (KO) mice, that these cytoprotective effects of EPO resulted from direct biological effects on the β cells, and that JAK2 is its essential intracellular mediator. We also show that endogenous EPO or JAK2 in β cells had no essential role in determining β-cell development or homeostasis. Given that epo is a target gene of the hypoxia inducible factor (HIF) pathway, we hypothesized that deletion of von Hippel Lindau (VHL), a negative regulator of this pathway, in the β cells would lead to enhanced transcription of HIF-target genes, which are largely pro-survival, and lead to enhanced β-cell mass and function. Contrary to our hypothesis, in Chapter VI, our results show that the epo gene is not expressed in islets. Furthermore, β cell-specific VHL KO mice were glucose intolerant due to impaired β-cell function and mass, which we were able to rescue with rHuEPO treatment. Our results demonstrate that EPO exerts direct biological effects on the pancreatic β cells. Further understanding of the biology of EPO may hold promise for the development of a potential novel strategy for diabetes prevention and treatment.

Keywords: erythropoietin
diabetes
pancreatic beta cell
Advisor: Woo, Minna