VictorJuiz/thesis huggingface dataset:
Determinism vs. Stochasticity in Community Assembly Processes: The Role of Species Phylogeny and Dominance

The deterministic or stochastic nature of the rules that regulate which species co-exist in a community has been long debated in ecology. This thesis aims to answer (1) if understanding the degree of determinism in the co-existence of species is more or less informative than other sources of uncertainty affecting regional biodiversity, (2) if biodiversity is important to understand ecosystem processes, and (3) if dominance and determinism are correlated. Using a landscape model I show that the degree of determinism or stochasticity (1) controls regional species richness, and (2) causes more uncertainty on species richness than land use change or climate change in the Tropical Andes. In herbaceous communities around the world, diversity is important to improve predictions of biomass productivity and litter accumulation mostly when the diversity and biomass descriptors of the communities were partitioned into legumes, forbs and graminoids. Graminoids, grasses and Carex, and one forb lineage were more likely to be dominant species than non-dominant, while more than a dozen forb lineages were more likely to be non-dominant species. The environment affected the dominant plants the most, increasing the role of habitat filtering, with a less common effect of limiting similarity; in contrast, non-dominant plants were mostly affected by limiting similarity among the non-dominants, but with no signal of habitat filtering. This pattern was observed in herbaceous systems using a local dominant removal experiment and a global observational dataset. The results show that dominant species are a more deterministic subset of species that converge towards a predictable optimum constrained by environmental conditions. In contrast, non-dominant species are better described as a diverging group of species, potentially with multiple optimums, and therefore with a less predictable response. Understanding the differences between dominant and non-dominants can improve models of ecosystem services that rely either on biomass accumulation or on diversity.

Keywords: determinism-stochasticity
dominant removal experiment
ecosystem services
landscape ecology
phylogenetic dispersion
plant community assembly
Advisor: Cadotte, Marc W
Nomads in Late Chalcolithic Northern Mesopotamia: Mobility and Social Change in the 5th and 4th Millennium BC

Due to the nature of their lifestyle and inherent mobility nomadic groups of the past have left little if any discernible imprint in excavated archaeological records. This is regrettable since most regions of the world that saw the emergence of complex societies were shaped by pastoralism as much as by agriculture, requiring us to study the modes in which nomadic and sedentary populations interacted with each other. My study addresses the transformative impact that nomadic groups had on Northern Syria and Northern Mesopotamia during the Early Late Chalcolithic period (4500 – 3800 BC), a crucial time span of social and technological innovations that foreshadowed the “Urban Revolution” of the 4th millennium BC. Using chaîne opératoire as underlying analytical tool I studied material assemblages from surveys and excavations across southeastern Turkey, Northern Syria, northern Iraq and Western Iran to identify items of material culture that can be associated with non-sedentary populations and their seasonal movements within this greater region. This study was complemented by detailed petrographic analyses of ceramics from key sites that had seen extensive excavation. My study not only contributes to a better regional understanding of Late Chalcolithic societies (notably the social and economic relationships between settlements and hinterland) but also provides a template for how to enhance the visibility of the “invisible nomad” within the archaeological record.

Keywords: Ceramic analysis
Late Chaloclithic
Mesopotamia
Movement
Pastoralism
Petrography
Advisor: Reichel, Clemens
Exploring the Role of Zirconia Surface Treatments on the Properties and the Material’s Bonding to Resin Cement

Objectives: 1. To evaluate the bond strength of yttria-tetragonal zirconia polycrystalline (Y-TZP), lithium-disilicate, and feldspathic ceramics to 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing and non-MDP resin cements. 2. To evaluate the effect of ultrashort-pulse laser (UPL) on surface treatment on Y-TZP surface properties, the material’s bond strength to resin cement, and the effect of thermal stress on bond strength. Methods: Lithium-disilicate (LD), feldspathic porcelain (FP), and Y-TZP blocks received surface treatment according to the manufacturer recommendations (LD and FP: hydrofluoric acid, Y-TZP: alumina-blasting), and were luted to human dentin using MDP-containing (UL) or non-MDP adhesive system (UN). Specimens were microtensile tested. Fully-sintered Y-TZP received either no treatment (CTL) or one treatment of: ALB, SIL, or UPL. UPL consisted of either dots (LSD) or lines (LSL) patterns. Surface roughness, contact angle, and crystalline phases were evaluated. Y-TZP were cemented to composite using resin-based cement combined with a silane and MDP-containing adhesive. Specimens were incubated for 48 hours, then microtensile tested directly or after thermocycling. Results: The type of ceramic and the resin cement both had significant effects on bond strength (P≤.001). Y-TZP showed significantly lower bond strength (p

Keywords: microtensile bond strength
surface characterization
thermocycling
Y-TZP
Advisor: Finer, Yoav
De Souza, Grace
The Reprogramming of White Adipose Tissue to Brown Adipose Tissue Mediates Adverse Metabolic Dysfunction After A Burn Injury

A burn injury represents one of the most severe forms of trauma and affects more than two million people in North America annually. Of all cases, nearly 4000 people die of complications related to the injury. A hallmark of severely burned patients is the activation of a hypermetabolic stress response, which is characterized by hyperglycemia, lipolysis, and protein catabolism. Perhaps the most serious gap in our understanding of the hypermetabolic response in burns is the role of the adipose tissue. Humans harbour two distinct adipose depots, white adipose tissue (WAT) and brown adipose tissue (BAT) that carry out essentially opposite functions. WAT is primarily involved in storing excess energy, whereas BAT burns excess energy in the form heat. This fat burning aspect of BAT has emerged as a powerful tool in combating the metabolic syndrome (hyperglycemia, excess body fat, hypertension). Additionally, it has been discovered that our WAT can be reprogrammed to become BAT, however, whether or not such reprogramming (white to brown fat) occurs after a burn injury is unknown. We therefore investigated the adipose tissue, and its role in post-burn hypermetabolism, by using an animal model of burn injury and tissue from clinical burn patients. In our first study, we report the reprogramming of WAT to BAT in both burn patients and post-burn mice indicated by increased expression of the brown adipocyte marker, uncoupling protein 1 (UCP-1). This reprogramming of WAT post-burn injury required both IL-6 and catecholamine secretion from alternatively activated macrophages. In our second study, we demonstrated that WAT browning with its associated lipolysis increased plasma levels of free fatty acids, leading to the accelerated development of hepatic steatosis and dysfunction after a burn injury. The last study of this thesis was geared towards clinical applications, and centered on the inhibition of the WAT to BAT switch via the use of an IL-6R blocker and propranolol to improve post-burn hypermetabolism and organ steatosis. In summary, our findings highlight an essential role of the adipose tissue in contributing to post-burn hypermetabolism and pathology.

Keywords: Adipose
Beige fat
Browning
Burns
Metabolism
Trauma
Advisor: Jeschke, Marc G
Chiral Donor-Functionalized N-Heterocyclic Carbenes for Asymmetric Catalytic Applications in Hydrogenation – From Design to Application

In this thesis, the synthetic protocol for a new class of enantiopure, primary-amine tethered N-heterocyclic carbene (NHC) ligands is described. The synthesis, coordination chemistry, and applications in catalysis for three ligands from this class with general formula (S,S)/(R,R)-H2N-CHPh-CHPh-NHC (NHC = -NCHCHN(C)R, R = Me, tBu, or Mes) are reported. The imidazolium salt of these ligands can be prepared in high yield and purity from the SN1 reaction between chiral sulfamidates and the corresponding N-substituted imidazoles. The method of coordination of the NHC ligands to metals depends on the acidity of the C-H functional in the imidazolium salts. Silver and copper compounds can be prepared in high yield with the ligand to the metal ratio of 2:1 or 1:1. Ruthenium, iridium, and rhodium complexes can also be prepared via transmetallation from the silver or copper reagents, intramolecular base deprotonation, or C-H oxidative addition. Four ruthenium complexes and two iridium complexes based on these ligands were proven active for ketone hydrogenation, under relatively mild condition (50℃, 25 bar H2(g)). Three half-sandwich ruthenium compounds containing Cp (cyclopentadienyl) or Cp* (1,2,3,4,5-pentamethylcyclopentadienyl) are highly active aryl and alkyl hydrogenation catalysts with TOF (turnover frequency) up to 67 s-1, TON (turnover number) up to 104, and ee (enantiomeric excess) up to 86%. An experimental and computational study of the half-sandwich ruthenium systems suggests that the heterolytic splitting of dihydrogen over the metal-amido bond and hydride transfer from the catalyst to the substrate can both be rate-determining. An alcohol-assisted mechanism was also calculated to explain the rate enhancement when the catalysis was conducted in polar, protic solvents such as 2-PrOH. A full experimental and computational study was also performed for a Fe(P-NH-P’) system. Similarly, heterolytic splitting and hydride transfer are the two most energy demanding transition states. In addition, the enantiodetermining step (EDS) of this asymmetric ketone hydrogenation catalyst was calculated, and the origins of enantioselectivity were summarized as steric repulsion, the high compressibility of the backbone, and H-bond contributed stabilization.

Keywords: Asymmetric Catalysis
Chirality
Computational Chemistry
Hydrogenation
Kaibene
N-Heterocyclic Carbene
Advisor: Morris, Robert H
Photo Control of Protein Activity Using Genetically Encoded Photoswitches

Many biological processes are governed by protein activities that are spatially and temporally regulated. Where (i.e.: in a particular cell type or subcellular organelle) and when (i.e.: in relation to a cue, or for what duration) a protein is active can dictate its biological role. Photo-control, in which a target protein is made sensitive to light, can be used to precisely match the spatial and temporal patterning of protein activity in living cells. However, photo-control of protein activity often requires extensive protein engineering. This thesis describes three unique approaches to achieve photo-control of protein activity, as well as biophysical data to guide design of new optogenetic tools based on a novel red light-switchable protein. Chapter 2 describes the design and characterization a photo-switchable fusion protein, in which a coiled coil forming motif (Ehelix) is inserted into a circular permutant of photoactive yellow protein (c-PYP). c-Ehelix-PYP forms domain-swapped dimers that bind tightly to a peptide motif, whereas the monomers are inactive, enabling a novel mechanism for photo-control. Chapter 3 describes a blue light controlled dominant negative inhibitor to the transcription factor CREB (opto-DN-CREB). opto-DN-CREB was designed by fusing a transcription factor inhibitor (A-CREB) to PYP and making complementary mutations to PYP using the software suite ROSETTA. We demonstrate that opto-DN-CREB binds selectively to CREB in the dark, and that photo-control of CREB activity in cells is possible. Chapter 4 uses phage display to select for light-switchable protein interactions. Small proteins that bind selectively to the light or dark states of PYP and Avena sativa light-oxygen-voltage domain (asLOV) were selected, characterized extensively in vitro. They were then used to control subcellular localization of a fluorescent protein reporter in eukaryotic cells. Chapter 5 describes the biophysical characterization of a small, soluble red light-switchable protein (GAF3). NMR characterization shows that GAF3 undergoes conformational changes upon red light irradiation and suggest key residues involved. Together, this work adds to the available optogenetic toolkit and to our fundamental knowledge in the engineering of photo-switchable proteins.

Keywords: Optogenetics
Protein design
Protein folding
Protein structure
Advisor: Woolley, Andrew
Reducing the impact of imported infections in Ontario

Public health must remain responsive to the population’s changing health needs. As Canada’s diversity grows through immigration, protecting the health of immigrants when they travel to visit friends and relatives (VFR) is one such need. Immigrants comprise a growing proportion of international travelers and experience disproportionate travel-related infectious disease morbidity and mortality. While many infections are preventable, few immigrant travelers access pre-travel health services, in part because they are not covered under provincial health insurance plans. In my dissertation, I present three studies designed to respond to current gaps in evidence regarding how immigrant travelers perceive and respond to travel health risks, and how to measure travel-related disease burden. In the first study, I use qualitative methods to explore how South Asian travelers in Peel region conceptualize travel health risks. I found that travelers face many health challenges when traveling but adjust their behaviours to avoid or minimize key risks where possible. Their responses to risks, however, can be constrained by competing concerns (e.g. rushed travel, wanting to avoid family conflicts, cost, and a desire to enjoy traditional cuisine). These results highlight the importance of the social context in which travelers make health decisions. In the second study, I use novel data linkages to evaluate the utility of health administrative data for identifying hepatitis A, malaria and enteric fever infections. While diagnostic codes were sensitive, and additionally identified individuals who were likely unreported to public health, I found that their predictive value for accurately identifying cases was low. These results caution against the use of health administrative data, on its own, for this purpose. In the third study, I use a matched cohort design to estimate the health care utilization and attributable cost of hepatitis A, malaria and enteric fever infections in Peel region. Over three years, 318 cases resulted in more than $2 million dollars in direct health care spending, and attributable medical costs ranged from $4,500 - $8,000 per case. These results highlight that travel-related infections require substantial resources for diagnosis and treatment as most medically-attended cases require inpatient health care. Together, results from this dissertation advance our understanding of the complex social settings in which immigrant travelers make health-related decisions, and identify how much these avoidable infections cost Ontario’s health care system. Findings point to concrete opportunities to reduce disease burden through tailored health promotion strategies that are sensitive to the unique challenges immigrant travelers face. Costing estimates provide necessary model parameters to explore the cost-effectiveness of policies designed to improve access to pre-travel health services for high risk travelers.

Keywords: burden
communicable disease
immigrant
surveillance
travel
visiting friends and relatives
Advisor: Crowcroft, Natasha S
Rosella, Laura C
Advanced Parabolic Equation-Based Propagation Modeling for Train Communication Systems

With the continuing expansion of metropolitan areas, the demand for efficient mass transportation systems is increasing accordingly. An emerging wireless technology for rail signaling, which can significantly improve the efficiency of light rail, subway, and high-speed train transit systems, is communication-based train control (CBTC). In CBTC systems, trains communicate wirelessly with wayside access points, which are connected to a central control station. A prerequisite for the deployment of such systems is the existence of a suitable propagation model, which can provide accurate path-loss predictions of corresponding wireless channels. This is of particular importance due to the safety-critical nature of rail signaling and the rapid, cost-effective nature of system deployment. This thesis presents an advanced propagation modeling tool, based on parabolic equation methods, to characterize radio wave propagation in realistic, complex railway environments. Concrete guidelines are provided on how to extract input models from point cloud data and what level of detail is necessary and sufficient to obtain results agreeing with measured data. Moreover, enhanced techniques dealing with geometrical variations of guideways and practical antenna patterns are presented. The accuracy and efficiency of the developed propagation model are demonstrated in various practical scenarios. Furthermore, a robust approach on extracting surrogate models from arbitrary tunnel geometries is proposed. The extracted surrogate models can lead to significant computational savings, especially in optimization studies where repetitive calls of the propagation model are required. The thesis also presents two hybrid propagation modeling techniques, aimed at achieving a better trade-off between accuracy, efficiency, and generality, via using the advantages of one method to compensate for the limitations of another and vice versa. Moreover, effects of uncertainty in the environment and experimental setup on the variability of predicted signal strength are investigated. A new approach that can incorporate wall roughness into the model is introduced. It can be applied to tunnels with arbitrary cross-section geometries and large-scale surface roughness. Finally, a physics-based optimization strategy is presented to optimize the placement of access points for train communication systems. The validity and usefulness of the proposed methodology are demonstrated in an actual deployment site of CBTC systems.

Keywords: Channel Modeling
Computational Electromagnetics
Finite-Difference Method
Parabolic Equation Method
Train Communication System
Wireless Communication
Advisor: Sarris, Costas D.
Modeling targeted therapy mechanisms and predictive biomarker discovery using human primary non-small cell lung cancer xenografts

Lung cancer, the leading cause of cancer-related deaths worldwide, has recently been recognized as a large collection of molecularly-defined diseases. Molecularly-targeted therapies are revolutionizing clinical care for some molecularly-defined lung cancers. Perhaps the best studied example is targeting activating mutations of the epidermal growth factor receptor (EGFR) gene. Tyrosine kinase inhibitors (TKIs) have significantly improved clinically outcomes in lung cancer patients with these activating EGFR mutations. However, EGFR TKIs are not a cure as the vast majority of patients develop resistance. Some mechanisms of resistance to EGFR TKIs have been discovered, such as the secondary mutation in EGFR known as T790M which occurs in approximately half of patients. Third-generation EGFR TKIs can effectively treat T790M-positive disease; nonetheless, resistance develops against these inhibitors as well. Optimal treatments for the remaining 50% of non-T790M mediated resistance have yet to be determined, complicated by the fact that some mechanisms of resistance have not yet been discovered. To help identify further sources of resistance against EGFR TKIs, I leveraged our patient-derived xenograft (PDX) models of NSCLC with EGFR activating mutations. First, I demonstrated that these PDXs recapitulate patients’ tumour morphology, molecular biomarkers, and responses to targeted therapies. Next, the mechanism underlying an unexpected response to the single-agent EGFR-targeting monoclonal antibody Cetuximab was determined in one of our models with de novo T790M mutation. A third study identified a novel mechanism of resistance against an EGFR TKI and a corresponding effective treatment. Lastly, the origin of acquired resistance was explored, identifying and characterizing a sub-population of cells very similar to cells that can tolerate EGFR TKI treatment and act as a reservoir from which resistance develops. The knowledge gained from these studies provides novel and potentially clinically actionable biomarkers of response to EGFR TKIs in EGFR-mutant NSCLC.

Keywords: Drug tolerance
EGFR
Lung cancer
Patient-derived xenografts
Resistance
Targeted therapy
Advisor: Liu, Geoffrey
Tsao, Ming S
Molecular and Device Engineering of Group 13, 14, 15 Phthalocyanines and Tetrabenzotriazacorroles for Organic Photovoltaic Applications

Phthalocyanines (Pcs) are a family of compounds that constitute a key building block of the organic photovoltaic (OPV) literature. Aside from their desirable optical and electronic properties, we are interested in Pcs because of their proven scalability and stability, unlike most organic semiconductors in literature. Although the Pc chromophores can chelate to almost all elements of the periodic table and conform to varying molecular structures, research in the context of OPVs has been largely concentrated on planar derivatives that chelate to metal centres without axial substituents. This render them molecularly unmodifiable hindering the understanding of structure-property-performance relationships of Pcs in the context of OPVs. In this dissertation, axially-bonding Pc compounds incorporating elements from groups 13, 14, and 15 into their cavities were engineered chemically by axial phenoxylation and by ring-contraction chemistry into tetrabenzotriazacorroles (Tbcs). The functionality of the modified molecules was also assessed in OPVs. Aluminum, silicon, and phosphorus were selected to represent tri-, tetra-, and penta- valent elements respectively. Series of axially-phenoxylated aluminum phthalocyanines (AlPcs) and silicon phthalocyanines (SiPcs) were synthesized, characterized, and incorporated into OPV devices. These easily prepared derivatives exhibited superior OPV performances in comparison to their baselines as electron acceptors. Tbcs which differ structurally from Pcs with the omission of a single imine nitrogen were unknown in the context of OPVs. This small difference in structure has paramount effects on the optical and electrochemical properties of the chromophore. For example, Tbcs exhibit a unique and desirable dual absorption of blue and red portions of the solar spectrum simultaneously. The first application of any Tbc compound in OPVs, oxy phosphorus tetrabenzotriazacorrole (POTbc) as a prototype, paired with conventional organic semiconductors is reported here. POTbc showed promise as an electron donating material due to its highly charged chromophore. POTbc was then coupled with boron subphthalocyanines (BsubPcs) as complementary absorbing donor-acceptor pairs in fullerene-free “black” OPVs. The outdoor stability of POTbc/BsubPc devices were assessed exhibiting on-par stability with their baseline. Further molecular structures of Tbcs, and resulting properties, were enabled through the synthesis of multiple Tbc derivatives chelating to a silicon center (SiTbcs).

Keywords: Electronics
Materials Chemistry
Photovoltaics
Phthalocyanines
Advisor: Bender, Timothy P.