VictorJuiz/thesis huggingface dataset:
Coupling Temperature Sensing and Morphogenesis in the Pathogenic Fungus Candida albicans

Temperature is a critical environmental signal, which exerts powerful control over the development and virulence of diverse microbial pathogens. Fungi, along with other microbial species, exploit a diversity of mechanisms to sense and respond to temperature fluctuations that may be encountered in the host or under other conditions of temperature stress. For Candida albicans, the leading fungal pathogen of humans, temperature influences mating, phenotypic switching, resistance to antifungal drugs, and the morphogenetic transition from yeast to filamentous growth. C. albicans morphogenesis is strongly influenced by temperature, and most filament inducing cues depend on a concurrent increase of temperature to 37˚C before morphogenesis can occur. Further elevated temperature of 39˚C to 42˚C can serve as an independent filament-inducing cue, although the molecular mechanisms underpinning this temperature-dependent morphogenetic transition remain largely uncharacterized. Here, I provide the first comprehensive investigation of the molecular mechanisms mediating temperature-dependent morphogenesis in C. albicans. I establish that the thermally responsive molecular chaperone Hsp90 orchestrates temperature-dependent morphogenesis, and that Hsp90 functions as a key temperature sensor, such that elevated temperature is required to relieve Hsp90-mediated repression of the morphogenetic program. Further, I demonstrate that Hsp90 controls morphogenesis via at least two distinct cellular signaling cascades. First, Hsp90 and its co-chaperone Sgt1 physically interact, and together regulate protein kinase A (PKA) signaling via an interaction with the adenylyl cyclase of the PKA cascade, Cyr1, such that genetic depletion of either Hsp90 or Sgt1 activates PKA signaling and induces filamentation. Second, Hsp90 controls temperature-dependent morphogenesis via previously uncharacterized cellular circuitry comprised of the cyclin-dependent kinase Pho85, the cyclin Pcl1, and the transcriptional regulator Hms1. Together, this research illuminates the central role of Hsp90 in coupling temperature sensing and morphogenesis in the human fungal pathogen C. albicans.

Keywords: fungal pathogenesis
molecular chaperone
Advisor: Cowen, Leah
Electrochemical Studies of DNA Films on Gold Surfaces

DNA-metal ion interactions are critical for stabilizing conformations of double stranded (ds) DNA and through specific binding sites will influence the interaction of DNA with other molecules. It has been shown that different metal ions bind to different sites within nucleic acids. Work in this thesis exploits the interactions of Zn2+ with nucleic acids that are linked to surfaces. Zn2+ can interact with the phosphodiester backbone and engage in interactions with the purine nucleobases. Electrochemical studies of ds-DNA films have demonstrated that in the presence of Zn2+ films containing a single nucleotide mismatch give rise to a specific electrochemical signature. Electrochemical impedance spectroscopy (EIS) allows the discrimination of mismatched DNA films from those that are fully matched by monitoring differences in the resistance of charge transfer. Scanning electrochemical microscopy (SECM) allows multiplexing of the data acquisition and monitoring of the current response I, which is attenuated as a function of mismatch. In this thesis, various potential factors were explored in detail that may impact the discrimination of nucleotide mismatches in ds-DNA films by EIS and SECM. These factors include the position of the mismatch, its type, the number of mismatches, the length of the DNA duplex, and the length of target sequences. In particular, when the two strands are of unequal length, the resulting nucleotide overhang may mask the mismatch signature. Such overhangs are expected in real biosensor applications, in which the DNA is isolated from cellular targets. Results presented here clearly demonstrate that mismatches are readily distinguished from fully matched strands even in overhang systems, suggesting that this approach has promise for realistic sensor applications.

Keywords: Electrochemical
Label free
Biosensor
DNA
Single nucleotide mismatch
Detection
Advisor: Kraatz, Heinz-Bernhard
Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

Keywords: drug delivery, controlled release, nanoparticles, polysaccharides, theranostics
Advisor: Wu, Xiao Yu
Non-holomorphic Cuspidal Automorphic Forms of GSp(4;A) and the Hodge Structure of Siegel Threefolds

Let V( ) denote a local system of weight on X = A2;n(C), where X is the moduli space of principle polarized abelian varieties of genus 2 over C with xed n-level structure. The inner cohomology of X with coe cients in V( ), H3 ! (X;V( )), has a Hodge ltration of weight 3. Each term of this Hodge ltration can be presented as space of cuspidal automorphic representations of genus 2. We consider the purely non-holomorphic part of H3 ! (X;V( )) denoted by H3 Ends(X;V( )). First of all we show that there is a non-zero subspace of H3 Ends(X;V( )) denoted by V (K), where K is an open compact subgroup of GSp(4;A), such that elements of V (K) are obtained by the global theta lifting of cuspidal automorphic representations of GL(2) GL(2)=Gm. This means that there is a non-zero part of H3 Ends(X;V( )) which is endoscopic. Secondly, we consider the local theta correspondence and nd an explicit answer for the level of lifted cuspidal automorphic representations to GSp(4; F) over a non-archimedean local eld F. Therefore, we can present an explicit way for nding a basis for V (K) for a xed level structure K. ii There is a part of the Hodge structure that only contributes in H(3;0) ! (X;V( )) H(0;3) ! (X;V( )). This part is endoscopic and coming from the Yoshida lift from O(4). Finally, in the case X = A2, if eendo(A2;V( )) denotes the motive corresponded to the strict endoscopic part (the part that contributes only in non-holomorphic terms of the Hodge ltration), then we have eendo(A2;V( )) = 􀀀s 1+ 2+4S[ 1 􀀀 2 + 2]L 2+1; (1) where = ( 1; 2) and is far from walls. Here S[k] denotes the motive corresponded to Sk, the space of cuspidal automorphic forms of weight k and trivial level, and sk = dim(Sk). ii

Keywords: Theta lifting
Siegel modular forms
Local theory
Advisor: Kudla, Stephen S.
Identifying Nursing Activities to Estimate the Risk of Cross-contamination

Hospital Acquired Infections (HAI) are a global patient safety challenge, costly to treat, and affect hundreds of millions of patients annually worldwide. It has been shown that the majority of HAI are transferred to patients by caregivers' hands and therefore, can be prevented by proper hand hygiene (HH). However, many factors including cognitive load, cause caregivers to forget to cleanse their hands. Hand hygiene compliance among caregivers remains low around the world. In this thesis I showed that it is possible to build a wearable accelerometer-based HH reminder system to identify ongoing nursing activities with the patient, indicate the high-risk activities, and prompt the caregivers to clean their hands. Eight subjects participated in this study, each wearing five wireless accelerometer sensors on the wrist, upper arms and the back. A pattern recognition approach was used to classify six nursing activities offline. Time-domain features that included mean, standard deviation, energy, and correlation among accelerometer axes were found to be suitable features. On average, 1-Nearest Neighbour classifier was able to classify the activities with 84% accuracy. A novel algorithm was developed to adaptively segment the accelerometer signals to identify the start and stop time of each nursing activity. The overall accuracy of the algorithm for a total of 96 events performed by 8 subjects was approximately 87%. The accuracy was higher than 91% for 5 out of 8 subjects. The sequence of nursing activities was modelled by an 18-state Markov Chain. The model was evaluated by recently published data. The simulation results showed that the high-risk of cross-contamination decreases exponentially by frequency of HH and this happens more rapidly up to 50%-60% hand hygiene rate. It was also found that if the caregiver enters the room with high-risk of transferring infection to the current patient, given the assumptions in this study, only 55% HH is capable of reducing the risk of infection transfer to the lowest level. This may help to prevent the next patient from acquiring infection, preventing an infection outbreak. The model is also capable of simulating the effects of the imperfect HH on the risk of cross-contamination.

Keywords: Hospital acquired infection
Infection control
Hand hygiene
Accelerometer
Nursing activities
Sony PlayStation
Sixaxis
Transition points
Recursive least squares
Adaptive segmentation
Mathematical modelling
Markov Chain
Advisor: Geoff, Fernie
An Exploration of the Relationship between Poverty and Child Neglect in Canadian Child Welfare

Objectives: Concerns have been raised that child welfare systems may inappropriately target poor families for intrusive interventions. The term “neglect” has been critiqued as a class-based label applied disproportionately to poor families. The objectives of the study are: to identify the nature and frequency of clinical and poverty-related concerns in child neglect investigations and to assess the service referral response to these needs; to examine the contribution of poverty-related need to case decision-making; and to explore whether substantiated cases of neglect can be divided into subtypes based on different constellations of clinical and poverty-related needs. Methods: This study is a secondary analysis of data collected through the 2008 Canadian Incidence Study of Reported Child Abuse and Neglect (CIS‑2008), a nationally representative dataset. A selected subsample of neglect investigations from the CIS‑2008 (N = 4,489) is examined through descriptive analyses, logistic regression, and two-step cluster analysis in order to explore each research objective. Results: Children and caregivers investigated for neglect presented with a range of clinical and poverty-related difficulties. Contrary to some previous research, the existence of poverty-related needs did not influence case dispositions after controlling for other relevant risk factors. However, some variables that should be, in theory, extraneous to case decision-making emerged as significant in the multivariate models, most notably Aboriginal status, with Aboriginal children having increased odds of substantiation, ongoing service provision and placement. Cluster analyses revealed that cases of neglect could be partitioned into three clusters, with no cluster emerging characterized by poverty alone. Conclusions: The majority of children investigated for neglect live in families experiencing poverty-related needs, and with caregivers struggling with clinical difficulties. While poverty-related need on its own does not explain the high proportion of poor families reported to the child welfare system, nor does it account for significant variance in case decision making, cluster analysis suggests that there exists a subgroup of “neglected” children living in families perhaps best characterized by the broader notion of social disadvantage. These families may be better served through an orientation of family support/family welfare rather than through the current residual child protection paradigm.

Keywords: child neglect
child welfare
poverty
child maltreatment
child welfare policy
Advisor: Fuller-Thomson, Esme
Energy Flow and Food Web Ecology along a Hydroperiod Gradient

Identifying the ecological mechanisms that determine food web structure is critical for understanding the causes and consequences of diversity. The objective of this thesis was to identify the mechanisms structuring aquatic food webs across environmental gradients from a multi-level perspective (individual to ecosystem) using integrative methodology and field experiments to test classic ecological theory. My results demonstrate support for the dynamic constraints hypothesis, which predicts habitats with greater disturbance should have shorter food chains, but are not consistent with the ecosystem size hypothesis that predicts larger ecosystems have longer food chains. Insect and amphibian richness increased with increasing pond size and hydroperiod, indicating that insertion of new consumers into pond communities was driving variation in food-chain length. A multivariate analysis testing the influence of physicochemical variables on food-web characteristics revealed that hydroperiod and pond area had a strong influence on amphibian and invertebrate assemblages, trophic diversity and 15N range. Food-chain length did not respond strongly to any one variable, but instead responded weakly to multiple environmental variables, suggesting interacting influences on food-web structure. Conversely, the trophic niche of amphibian larvae was not influenced by pond hydroperiod, but did exhibit ontogenetic diet shifts. Populations of amphibian larvae with broader niche widths also had increased individual variation, supporting the niche variation hypothesis. In addition, I assessed whether species diversity influenced the magnitude of cross-habitat resource flow between aquatic and terrestrial habitats via emerging aquatic insects, metamorphosing amphibians, and litter deposition. Deposition into ponds far exceeded carbon exported via insect and amphibian emergences. We found a negative relationship between resource flux and the diversity of amphibians and insects, which contradicts the general pattern of positive biodiversity-ecosystem function relationships. My research strongly suggests environmental variation is a key process in shaping food-web structure and function and that multiple methodologies are needed to understand temporal and spatial dynamics of aquatic ecosystems.

Keywords: aquatic
stable isotopes
amphibians
invertebrates
disturbance
wetland
Advisor: Williams, D. Dudley
Attentional Filtering in Young and Older Adulthood

To date, research on cognitive aging has treated attention as a unitary resource that operates according to a single mechanism of top-down selection. However, contemporary theoretical models of attention propose that it is a distributed resource, embedded in distinct cortical subsystems, and operates in a manner that reflects the properties of those subsystems. For instance, perceptual attention is thought to originate in posterior sensory subsystems and filter competing unattended input prior to encoding, resulting in early selection of attended information. Executive attention, by contrast, is thought to originate in frontal control subsystems and filter unattended input after encoding, resulting in late selection of attended information. Guided by a distributed resource model, the work described here focuses on how healthy advanced aging influences early selection mechanisms embedded in posterior subsystems, perceptual encoding, and the relationship with frontal subsystems mediating late selection. To examine perceptual attention in isolation, object discrimination tasks were devised in which perceptual competition between repeated objects was manipulated while holding demand on executive control constant. Cortical mechanisms of early selection were probed using functional magnetic resonance imaging (fMRI) indices of neural response and adaptation. Evidence of an age-related impairment in early selection was detected across two fMRI experiments. Unlike young adults, unattended objects not only interfered with perceptual encoding in older adults, but were co-encoded along with the contents of attended input. Age impairments in early selection were also associated with greater reliance on frontally-mediated late selection resources, and, reduced functional connectivity with basal forebrain nuclei. In sum, the results indicate that with increasing age, frontal control subsystems become increasingly encumbered with compensatory redistribution of function from the perceptual cortices, possibly due to loss of central cholinergic integrity. Many well-described age-related deficits of executive attention may therefore represent a consequence of impaired early selection, rather than its cause.

Keywords: attention
aging
perception
neuroimaging
Advisor: Rosa, Eve De
The Effect of an Individualized Education Intervention versus Usual Care on Pain following Ambulatory Inguinal Hernia Repair

Inguinal hernia repair (IHR) is a common ambulatory surgery procedure performed in Canada, after which many patients experience moderate to severe pain. Limited research has been found that examines interventions to reduce pain following ambulatory surgery, and none specifically for patients undergoing IHR. This trial evaluated the effectiveness of an individualized Hernia Repair Education Intervention (HREI) for patients following this ambulatory surgery. Participants (N= 82) were randomized to either the intervention or usual care group pre-operatively in the pre-admission clinic. The HREI included a booklet about managing pain and face-to-face session to discuss its content, and two telephone support calls (before surgery and 24 hours after surgery). The primary outcome was WORST 24 hour pain intensity on movement on post-operative day 2. Secondary outcomes included pain intensity at rest and movement, pain–related interference with activities, pain quality, analgesics taken, and adverse effects at post-operative days 2 and 7. At day 2, the intervention group reported significantly lower scores for all pain intensity outcomes, including WORST 24hr pain on movement (t (df) = 4.7 (73), p< 0.001), WORST 24 hr pain at rest (t (df) = 3.8 (73), p < 0.001), pain NOW at rest (t (df) = 3.3 (73), p = 0.001) and on movement (t (df) = 3.4 (73), p = 0.001). Also on day 2, pain-related interference scores for the intervention group were lower than the usual care group but not significantly different with the bonferroini correction (t (df) = 2.1 (73), p=0.04). The intervention group took significantly fewer opioids on day 2 (t (df) = 3.0 (73), p=0.004). Although there were no differences in any of the pain or interference outcomes on day 7, 36% (n=26) of the total sample reported moderate-severe pain at day 7. Constipation was the adverse effect identified most often, by both groups, on both days 2 and 7.This intervention was effective at post-operative day 2 but revisions need to be made to the intervention to assess for outcomes over a longer period of time.

Keywords: Inguinal Hernia Repair
Pain
Ambulatory Surgery
Patient Education
Advisor: Watt-Watson, Judith Heather
Thermodynamic Studies of Halogen Bonding in Solution and Application to Anion Recognition

Halogen bonding (XB), the interaction between electron deficient halogen compounds and electron donors, is an established non-covalent interaction in the solid and gaseous phases. Understanding of XB in the solution phase is limited. This thesis describes experimental studies of XB interactions in solution, and the application of XB interactions in anion recognition. Chapter 1 is a brief review of current understanding of XB interaction: theoretical models, studies of XB in solid and gaseous phases and examples in biological systems are discussed. At the end of this chapter, halogen bonding in the solution phase is discussed, along with applications of halogen bonding in organic syntheses. In chapter 2, linear free energy relationships involving the thermodynamics of halogen bonding of substituted iodoaromatics are studied. The utility of substituent constants and calculated molecular electrostatic potential values as metrics of halogen bond donor ability are discussed. Density Functional Theory (DFT) calculations are shown to have useful predictive values for trends in halogen bond strength for a range of donor-acceptor pairs. Chapter 3 describes the development of new multidentate anion receptors based on halogen bonding. Bidentate and tridentate receptors were found to exhibit significantly higher binding constants than simple monodentate donors. These receptors show selectivity for halide anions over oxyanions. Using 19F NMR spectra at different temperature, the enthalpies and entropies of anion bindings for monodentate and tridentate receptors were determined. The results indicate a positive entropy contribution to anion binding for both mono and tridentate receptors in acetone solvent. Finally in chapter 4, some mesitylene based receptors with 3-halopyridinium and 2-iodobenzimidazolium donors are introduced. The receptors perform halide anion recognition in aqueous solvent system through charge-assisted XB interactions. These findings can allude to utility in organic synthesis, supramolecular chemistry and drug design.

Keywords: Halogen bonding
anion receptor
solvent effect
molecular recognition
halide receptor
mesitylene
Advisor: Mark, Taylor