VictorJuiz/thesis huggingface dataset:
Theory of Charge and Heat Transport Mechanisms in Nanodevices
Keywords: Buttiker probe
Feynman-Vernon path integral
Molecular junction
Nanodevices
Quantum heat machine
Quantum thermal transport

In this thesis, we pursue mechanisms in the nonequilibrium transport of charge and heat, to elucidate nanodevice operation, and explore fundamental theoretical questions. The thesis is divided into two parts. Part I explores in detail the role of incoherent effects on the charge transport behaviour of molecular junctions. Such effects, induced by molecular vibrations, solvent or other environmental effects, play a crucial role in many physical setups, but are difficult to simulate explicitly. We apply the Landauer-B\"uttiker probe technique, a phenomenological approach that incorporates incoherent effects at a low computational cost, and demonstrate the applicability of the technique by verifying that it captures a number of pertinent physical features, and achieves semi-quantitative agreement with experimental data. Going beyond this, we apply the probe method to a number of proposed physical setups. In stacked vs. alternating GC-rich ds-DNA, we find the even-odd effect in the experimentally observed conductance can be explained via a mixed coherent-incoherent transport mechanism. We find that in general, environmental interactions are destructive to the operation of molecular charge rectifiers, though in certain circumstances a weak rectifying behaviour might arise from many-body environmental effects. In Part II of this thesis we shift our focus to heat transport, and particularly the operation of quantum heat machines. We begin with a study of the role of so-called noise-induced coherences on the operation of a quantum absorption refrigerator. While in the past quantum coherences have usually been found to boost power in such setups, we observe a complete shutdown of the device when coherences survive to the nonequilibrium steady-state. We then extend our analysis, developing a general approach that one can use to more easily discover the role of coherences in quantum heat machines. We conclude with the development of a new numerically exact approach, the iterative full-counting statistics path integral (iFCSPI), which is suitable for simulations of heat transport in nanodevices. The iFCSPI allows the calculation of the cumulants of heat transport, as well as strong-coupling and non-Markovian effects, provided it can be converged.
Thinking of You: The Interpersonal Work Meaningfulness Model
Keywords: Family member
Social factor
Work meaningfulness

A growing literature indicates that people are desired to experience a sense of positive work meaning. Although the topic on the antecedents of work meaningfulness is relatively well studied, we know comparatively little about how other people affect an individual’s sense of it. To deepen our understanding of how other individuals, especially significant others, shape meaningfulness attached to different work aspects and, subsequently, work outcomes, this dissertation proposed an Interpersonal Work Meaningfulness Model and empirically tested it using three types of family members as examples of significant others. Drawing on research of relational goals and relational self, I predicted that thinking of certain relational others influence work meaningfulness attached to certain work aspects, which in turn influence work outcomes. I contribute to our understanding of the antecedents of work meaningfulness by considering the relational nature of human beings and argue that an individual’s interdependent-self construal should be considered in understanding his or her sense of meaning attached to different work aspects. Pilot Test 1 qualitatively studied the content of work meaningfulness. In Pilot Test 2 I explored the relational goals that employees typically held with family members. Four main studies were conducted. The first study adopted a cross-sectional multi-source survey design to test the relationships among chronic thought of family members, work meaningfulness, and work outcomes. The second through fourth studies used experimental design and examined how the activated thought of family members influenced work meaningfulness and behavioral intentions. My findings suggested that thinking of family members could influence work meaningfulness, but the strength and pattern of such influence were not clear. The results of Study 1 through Study 3 suggested the important role of chronic thoughts of family members on work meaningfulness. The results of Study 2 and Study 3 indicated that the strength of interpersonal goal could moderate the effect of activated thought of family member on work meaningfulness. In addition to reporting the results, this dissertation discussed its scholarly contribution.
Investigating Antipsychotic Drug-induced Impairment of Central Energy Homeostasis
Keywords: Antipsychotic
Diabetes
Hypothalamus
Insulin
Olanzapine
Schizophrenia

Antipsychotic medications are increasingly linked to the development of insulin resistance and type 2 diabetes. Though antipsychotic-induced weight gain was initially thought to be responsible for these effects, evidence has shown that antipsychotics can impair glucose homeostasis separate from changes in adiposity. The majority of studies investigating the direct effects of antipsychotics on glucose homeostasis have examined peripheral changes; however, the central nervous system (CNS) also plays a vital role in the regulation of whole-body energy homeostasis. A handful of studies have looked at the association between the CNS and antipsychotic-induced glucose dysregulation but have not reported a direct association between CNS insulin and whole-body glucose homeostasis. Furthermore, a mechanism is far from established. Thus, we set out to determine if antipsychotics impair central insulin sensing, and whether this impairment was via action on the central KATP channel, a downstream signal of CNS insulin action. Use of the pancreatic euglycemic clamp technique allowed determination of glucose kinetics, while central infusion allowed determination of specific CNS effects. We discovered that the commonly used antipsychotic, olanzapine, impairs the ability of CNS insulin to suppress hepatic glucose production. We also discovered that olanzapine blocks KATP channel activation, preventing the CNS KATP channel from increasing glucose uptake. These divergent results suggest olanzapine can act on multiple pathways in the CNS to dysregulate whole body glucose homeostasis. We also investigated whether antipsychotics could directly modulate the hypothalamus, the primary brain region involved in energy homeostasis, using immortalized hypothalamic neurons from rats and mice. Use of a neuronal model minimized confounding effects present in whole-body research, such as antipsychotic-induced hyperglycemia and hyperinsulinemia. We determined that the antipsychotics olanzapine, clozapine, and aripiprazole can directly modulate insulin, energy sensing, and inflammatory signals in hypothalamic neurons. Taken together, our findings suggest that antipsychotics can directly modulate the CNS to dysregulate whole body energy homeostasis, via action on insulin and the KATP channel. This underlines the importance of including the CNS in future studies on antipsychotic-induced metabolic effects. Understanding this relationship has the potential to then be leveraged to develop new strategies to improve metabolic outcomes in patients with schizophrenia.
Age and Ageism in the Assessment of Witnesses
Keywords: Ageism
Aging
Credibility
Judicial Decision Making
Law
Law of Evidence

As Canada’s population ages, an area of related concern is widespread and systemic discrimination against older adults known as ageism. Despite its importance, little is known about the ways age or ageism relate to judges’ credibility decisions in common law trials. This study empirically examines case law to see if there is a relationship between old age and judges’ credibility decisions for a sample of witnesses (N=898). T-tests and probit regressions showed a positive correlation between old age and judges’ assessments of general credibility, where witnesses aged over 60 were more likely to be positively assessed. At the same time, testimony from witnesses who were aged over 60 was also less likely to be positively assessed in terms of weight. The other evidence led by the party that called a witness was the strongest predictor of judges’ assessments. When the inquiry is shifted to the texts of individual cases, there are examples of judges holding stereotypical beliefs about older individuals who testify in their courtrooms. The final part of this dissertation moves beyond credibility decisions and considers the ways the rules of evidence and procedure could disproportionately exclude older adults from participating in trials. While the rules are capable of accommodating witnesses who experience limitations, a case law review finds that these provisions are rarely used for older adults. Through its detailed catalogue of judicial behaviours and analysis of rules and procedure, this study provides insights into the ways age and ageism could affect older witnesses, a conclusion with that has implications for research as well as for those who practice law.
Normothermic Ex-Situ Liver Perfusion and PPAR-gamma Activation as Strategies to Reduce Liver Ischemia Reperfusion Injury
Keywords: Donation after circulatory death
Ischemia reperfusion injury
Kupffer cells
Liver biomarkers
Liver transplantation
Normothermic ex situ liver perfusion

The liver ischemia-reperfusion injury (IRI) is a significant problem during liver transplantation. IRI leads to hepatocyte damage and a prominent inflammatory response that results in graft dysfunction, and high morbidity and mortality following transplantation. The pro-inflammatory Kupffer cell (KC) polarization and the cold ischemic injury are key factors that initiate and perpetuate the severity of IRI. In this dissertation, I explore strategies that address these factors. First, I aim to modify the pro-inflammatory KC-phenotype in an in-vitro and in-vivo model. Second, I focus on optimizing a model of normothermic ex-situ liver perfusion (NEsLP) as a preservation technique to reduce cold ischemic injury and as a platform to evaluate the liver viability before transplantation. The pro-inflammatory (M1) activation of KCs is thought to initiate the IRI event. In this dissertation, I utilize a peroxisome proliferator activated-receptor-gamma (PPAR-γ) agonist to ameliorate the M1 polarization of KCs. The PPAR-γ activation results in a significant decrease of the M1-Nitric oxide + KC-phenotype in-vitro (Chapter 3) and in-vivo (Chapter 4), which reflects in a significant reduction of hepatocyte injury, apoptosis and necrosis in a mouse model of IRI. As the next step in this dissertation, I aim to optimize NEsLP for its use in donation after circulatory death (DCD) organs. In Chapter 6, I evaluate the different clinical perfusates to identify the most suitable solution for the perfusion of DCD grafts. The use of a human albumin/ dextran solution during NEsLP displays a better endothelial function and reduces the levels of AST, apoptosis, and necrosis after transplantation compared to the other solutions. Finally, in Chapter 7, I evaluate the feasibility of using NEsLP biomarkers to predict liver viability after transplantation with marginal DCD grafts. The model identifies consistent biomarkers of hepatocellular (lactate clearance and urea production) and biliary viability (bile/perfusate glucose and sodium ratio) that reflect in successful liver transplantation. The results of this dissertation highlight the importance of addressing several targets during IRI and suggest that the combination of these strategies evaluated by consistent viability biomarkers during NEsLP might result in a reliable use of marginal DCD grafts in the future.
Protein-protein Interaction Network Alignment and Evolution
Keywords: evolution
interactomics
interface-interaction network
network alignment
protein-protein interaction
systems biology

Network alignment is an emerging analysis method enabled by the rapid large-scale collection of protein-protein interaction data for many different species. As sequence alignment did for gene evolution, network alignment will hopefully provide new insights into network evolution and serve as a new bioinformatic tool for making biological inferences across species. Using new SH3 binding data from Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens, I construct new interface-interaction networks and devise a new network alignment method for these networks. With appropriate parameterization, this method is highly successful at generating alignments that reflect known protein orthology information and contain high network topology overlap. However, close examination of the optimal parameterization reveals a heavy reliance on protein sequence similarity and fungibility of other data features, including network topology data, an observation that may also pertain to protein-protein interaction network alignment. Closer examination of interactomic data, along with established orthology data, reveals that protein-protein interaction conservation is quite low across multiple species, suggesting that the high network topology overlap achieved by contemporary network aligners is ill-advised if biological relevance of results is desired. Further consideration of gene duplication and protein binding sites reveal additional PPI evolution phenomena further reducing the network topology overlap expected in network alignments, casting doubt on the utility of network alignment metrics solely based on network topology. Instead, I suggest a new framework to think about protein-protein interaction network alignment focused on generating and validating small-scale inferences. I create a prototype alignment visualization and analysis tool to facilitate this approach, which will hopefully aid researchers in learning more about the mechanisms of network evolution and how network alignment can model them.
The Application of Natural Abundance Carbon Isotope Ratio Analysis to Study Brain Fatty Acid Metabolism
Keywords: carbon isotope ratio analysis
Docosahexaenoic acid
fatty acid metabolism
Isotope ratio mass spectrometry
lipid metabolism
stable isotope

Over the past two decades, an increasing amount of experimental evidence has linked altered brain n-3 polyunsaturated fatty acid (PUFA) metabolism to neurological and neuropsychiatric diseases. Observational studies have associated low dietary n-3 PUFA consumption with an increased risk of brain disease, implicating a potential role for diet in modulating brain fatty acid metabolism. Unfortunately, many of the currently available methods to investigate the role of diet on brain fatty acid metabolism are limited by their reliance on tracer compounds. The research carried out in this thesis explores the novel application of natural abundance carbon isotope ratio analysis to study brain fatty acid metabolism. Based differences in brain DHA carbon isotope ratios (13C/12C, referred to as δ13C signatures), we differentiated between incorporation of dietary preformed DHA, and that which had been synthesized from the precursor α-linolenic acid, as brain δ13CDHA signatures reflected the dietary source. We then showed that natural abundance carbon isotope ratio analysis can be used to measure brain DHA turnover. When the n-3 PUFA tissue stores of mice were isotopically equilibrated to a background diet and then switched to a diet where n-3 PUFA have a different δ13C signature, the corresponding changes in brain δ13CDHA signatures reflected the turnover of brain DHA. Estimated brain DHA half-lives were found to be consistent with previous estimates based on different methodologies. Lastly, we extended the application of natural abundance carbon isotope ratio analysis to measure the contribution of within brain lipogenesis to brain palmitate levels. Based on δ13C signatures of dietary sugars and palmitate, and the established brain δ13CPAM signature from mice equilibrated to these carbon sources, we estimate that nearly half of the brain palmitate was synthesized within the brain. Collectively, the research conducted in this thesis has generated convincing data to validate the application of natural abundance carbon isotope ratio analysis for the study of brain fatty acid metabolism.
From DNA Topology to Pubertal Onset: Using Integrative Genomic Approaches to Study Transcriptional Regulation
Keywords: chromatin structure
DNA topology
genome-wide association studies
integrative genomics
next-generation sequencing
transcriptional regulation

Studying how cellular transcriptional programs are precisely controlled is essential for understanding development and disease. In this thesis, I first explore an essential aspect of transcriptional control: DNA topology. Topoisomerase II (TOP2) proteins regulate DNA topology by creating transient double-strand breaks. Topoisomerase II beta (TOP2B) facilitates gene transcription and is essential for postnatal development. However, the genome biology of TOP2B remains largely unknown. Through integrative analyses of the genome-wide binding profiles of TOP2B and many other transcriptional regulators, I discover that TOP2B associates with DNase I hypersensitive sites, tissue-specific TF binding, and evolutionarily conserved enhancers in the mouse genome. Particularly, TOP2B coincides with CTCF and cohesin, with a structural ordering at topologically associating domain (TAD) boundaries. I conclude that TOP2B is positioned to solve topological problems at critical cis-regulatory regions and its highly ordered binding is a prevalent feature of CTCF/cohesin sites flanking TAD boundaries. Next, we applied three gene expression profiling methods and integrative bioinformatics approaches to study the expression of genes associated with pubertal onset. Timing of pubertal onset varies in the general population and is associated with diverse later-life health outcomes. Studies of pubertal disorders and genome-wide association studies (GWAS) have identified hundreds of puberty-associated genes. However, their specific functions are not well characterized. To address this problem, I first showed that the expression of these puberty-associated genes is enhanced in multiple neuronal tissues using a human transcriptome dataset. We then used a sensitive qPCR platform to profile the mouse orthologs of these selected genes (n=179) in several mouse tissues during postnatal development in both sexes. To expand beyond the selected genes, we developed an automated 3’UTR-seq method to characterize changes of the transcriptome during postnatal development in mouse pituitary samples. My analyses have revealed abundant tissue-, age-, and sex-specific expression patterns of puberty-associated genes. These findings not only inform future functional studies but also provide valuable insights into the transcriptional regulation of the onset of puberty. Focusing on two distinct biological problems, my thesis explores the usage of integrative genomic approaches in studying transcriptional regulation.
Mediating for Immediacy: Text, Performance, and Dramaturgy in Multimedia Shakespeare Editions
Keywords: Apps
Digital Humanities
Pedagogy
Performance
Shakespeare
Technology

This dissertation examines digital multimedia Shakespeare editions, a group of seven projects that combine a complete Shakespeare text (plays or poetry) with a complete performance recording (audio or video). I argue that these projects constitute a new form of edition, which uses performance to engage new users and to supplement users’ understanding of Shakespeare’s text. By placing text and performance as congruent and contiguous elements in a digital interface, these projects transpose performance into the experiential framework of reading, enabling users to set their own pace and direction, and to navigate between reading and spectating. Through its multimedial format, this emerging category also expands the responsibilities of the editor or editorial team, shifting their role from a focus on text to include dramaturgy, pedagogy, and digital design. While these projects do make Shakespeare’s works accessible in new ways, they also reinforce existing narratives, in particular the tendency to regard Shakespeare’s text as dense and alienating while viewing performance as transparent and engaging. The aim of this dissertation is to explore the intellectual and aesthetic frameworks underlying these projects, as well as to articulate some critiques and possibilities for future development. My goal is to propose a set of guidelines for an editorial apparatus that would govern an edition that comprises not only text, but also performance and digital design.
Induced Abortion in Ontario
Keywords: adverse event
induced abortion
intergeneration
teen pregnancy
termination of pregnancy
venous thromboembolism

Induced abortion is one of the most commonly performed procedures among women of reproductive age. Most induced abortions occur in women experiencing unintended pregnancies, largely for non-medical reasons. To maximize a woman’s health and wellbeing, it is important to not only identify factors that heighten her need for induced abortion, but any negative consequences that may follow, including those directly related to the induced abortion procedure and the provider performing it. To address these points, three population-based studies were completed using data within Ontario’s publicly funded health care system, where induced abortion is legal and funded by the province’s health insurance plan. Project 1 investigated the intergenerational pattern of induced abortion between a mother and her teenage daughter. Project 2 examined the relation between induced abortion and the risk of venous thromboembolism soon after the procedure. Project 3 evaluated the surgical procedure volume of physicians who perform induced abortion and the associated risk of adverse outcomes following surgical induced abortion. Project 1 found that a teenage daughter is nearly twice as likely to have an induced abortion if her mother has had one. The greater the number of induced abortions a mother has had, the more likely her daughter is to have one as a teenager. Project 2 showed that up to 42 days after an induced abortion, a woman’s risk of having a diagnosed venous thromboembolism event is nearly double the risk of a woman without a recent pregnancy, although the risk is significantly lower than that after a livebirth. Project 3 observed that women whose surgical induced abortion is performed by a physician with a low procedure volume have an increased risk of experiencing an adverse event within 42 days after the procedure; however, adverse event rates vary widely between physicians, and are only partly explained by physician procedural volumes. This body of research may guide clinical, research and health policy efforts aimed to both reduce unintended pregnancy among young women, and improve the quality of care provided to women who receive abortion care.