VictorJuiz/thesis huggingface dataset:
The Mechanisms Underlying Free Fatty Acid-induced Hepatic Insulin Resistance

Elevated circulating free fatty acids (FFA) cause hepatic insulin resistance; however, the mechanisms for this process are incompletely understood. The objective of the studies in the thesis was to examine whether protein kinase C (PKC)-delta (d), oxidative stress, and the serine kinase IkBa kinase (IKK) B are causally involved in FFA-induced hepatic insulin resistance. To test this, we infused rats with lipid with or without inhibitors of the aforementioned factors for 7h, during the last 2h of which a hyperinsulinemic-euglycemic clamp was performed. In Study 1, inhibition of hepatic PKC-d using antisense oligonucleotide prevented FFA-induced membrane translocation of PKC-d, which is a marker of its activation, in parallel with prevention of lipid-induced hepatic insulin resistance, without affecting lipid-induced peripheral insulin resistance. These results implicate PKC-d as a causal mediator of FFA-induced hepatic insulin resistance. In Study 2, the antioxidant N-acetyl-L-cysteine (NAC) prevented lipid-induced hepatic insulin resistance in conjunction with reversal of lipid-induced increase in markers of IKKB and c-Jun NH2-terminal kinase 1 (JNK1) activation, and of impairment of insulin signaling, without affecting PKC-d membrane translocation and increase in phosphorylated p38 mitogen-activated protein kinase (MAPK) induced by lipid infusion. These findings suggested that oxidative stress is a causal mediator of lipid-induced hepatic insulin resistance upstream of IKKB and JNK1, and potentially downstream of PKC-d and p38 MAPK. In Study 3, sodium salicylate, an IKKB inhibitor, prevented FFA-induced hepatic insulin resistance via restoration of hepatic insulin signaling, thus implicating IKKB as a causal factor in the process. Together, the results from these studies demonstrate that PKC-d, oxidative stress, and IKKB are causally involved in FFA-induced hepatic insulin resistance and suggest that the sequence for the process is: FFA -> PKC-d -> oxidative stress -> IKKB -> impaired hepatic insulin signaling.

Keywords: Hepatic Insulin Resistance
Diabetes Mellitus
Free Fatty Acids
Oxidative Stress
PKC-Delta
Inflammation
Obesity
Advisor: Giacca, Adria
Knowledge Management Systems and Customer Knowledge Use in Organizations

The objective of the research was to understand how customer knowledge was used in an organization and the role knowledge management systems (KMS) played in this use. Traditionally, organizations have relied on internal knowledge to shape their corporate strategy. Recently however they are tapping new sources of knowledge that are external to the firm. One important source of organizational knowledge is a company’s customers, as they present a source of knowledge that may provide new insights, innovations and ideas that are not necessarily found within the organization. The study examined the perceptions and beliefs of customer knowledge held by an organization’s employees, the types of customer knowledge available to the firm, the use of a KMS, and its impact on an organization’s use of knowledge. We posed the question of how these perceptions and beliefs influenced the types of customer knowledge available and the design and implementation of a KMS. Furthermore, we investigated the impact of customer knowledge types and knowledge management systems on how an organization uses customer knowledge in its regular operational routines. To answer these questions, a case study was conducted in a Canadian health care systems organization. By taking the approach that individuals in an organization are the key to sharing knowledge with customers, this research was able to gain an in-depth understanding of how employees view customer knowledge, including both positive and negative attitudes towards this new source of knowledge. The types of customer knowledge available to the study organization were identified, as were the ways that the newly implemented KMS helped and hindered knowledge sharing. The results of the research demonstrate how the types of customer knowledge available to an organization can be categorized by the perceived quality and the perceived accessibility of the knowledge. These findings contribute to the field of knowledge management by moving towards a theory of how customer knowledge is used by an organization, and how internal and external factors affect this use. Furthermore, this study raises awareness of the importance of a KMS in managing customer knowledge, including key aspects of its design and implementation.

Keywords: Information Systems
Knowledge Management
Advisor: Choo, Chun Wei
Upregulation of CaMKIIβ and Nogo-C mRNA in Schizophrenia and the Prevalence of CAA Insert in the 3’UTR of the Nogo Gene

Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, cDNA library subtractive hybridization experiments using post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were performed. I found the mRNA of two neurodevelopmentally important genes, Nogo (RTN4) and calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ), to be overexpressed in post-mortem frontal cortex tissues from patients who suffered with schizophrenia. I used the quantitative real-time polymerase chain reaction method to determined the mRNA levels of these genes in tissues from age- and sex-matched individuals. Nogo is a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The gene produces three splice variants, Nogo-A, B and C. I found Nogo-C mRNA to be overexpressed by 26% in schizophrenia. I also found a 17% reduction of Nogo-B mRNA in samples from individuals who had been diagnosed with severe depression. Furthermore, I showed that there is a direct correlation between the expression of both Nogo-A and -C and the presence of a CAA insert in the 3’UTR of the Nogo gene. CaMKII is a kinase localized at the postsynaptic density. The holoenzyme is primarily composed of the subunits α and β, encoded by two separate genes. It influences the expression of many neuroreceptors, in particular receptors of the glutamatergic pathway. CaMKII also mediates neural maturation during puberty, a time of onset of schizophrenia. The expression of CaMKIIα was elevated 29% in frontal cortex tissues of patients who suffered from depression. The expression of CaMKIIβ was elevated 27% in tissues of schizophrenia patients and 36% in tissues of patients diagnosed with depression. Upregulation of CaMKIIβ was associated with the presence of the CAA insert in at least one copy of the Nogo gene in a group containing both healthy subjects and patients with mental illness, possibly linking the CaMKII and Nogo pathways. The values for the expression of Nogo, CaMKIIα and CaMKIIβ were normalized to β-glucuronidase expression to minimize the effects of mRNA degradation. These results confirm that upregulation of Nogo-C and CaMKIIβ is likely associated with schizophrenia.

Keywords: CaMKII
schizophrenia
Nogo
RTN4
human
frontal cortex
gene variant
gene expression
Advisor: Seeman, Philip
The Search for Genetic Structure and Patterns in Vietnamese Frogs

Vietnam has the greatest biodiversity of any country in Indochina. This diversity may be due to its topographically complex nature, with hills and mountains, drained by several independent river systems, covering three quarters of its area. Topographic complexity has undoubtedly had profound effects on the flora and fauna of the region. Recent surveys have uncovered several cryptic species in what were previously considered single widespread species. These discoveries have led some researchers to propose that widespread forest species do not, in fact, exist in Southeast Asia. To test these hypotheses, I examined patterns of mitochondrial phylogeny in several groups of frogs, both at and below the species level. Additionally, these analyses helped clarify the otherwise chaotic picture of anuran taxonomy and systematics. The stream–tied waterfall frogs of the genera Amolops and Odorrana were examined, the monophyly of the ranid subfamily Amolopinae was rejected, and taxonomic adjustments were made. The phylogeny of the Vietnamese narrow–mouthed frogs of the genus Microhyla was recovered and the current taxonomy examined. Patterns of maternal dispersal and genetic differentiation in mitochondrial DNA were further examined within Microhyla heymonsi, revealing geographic structuring and the existence of two sympatric lineages. Lastly, frogs of the Polypedates leucomystax complex were examined and two major, largely sympatric lineages recovered. Within these groups, 11 separate mitochondrial lineages identified. These represented separate species on the basis of advertisement call and allozyme evidence. The relationship of genetic differentiation and river systems was also investigated and common patterns among the different groups were explored. Clear genetic breaks occurred across both the Red River and the Annamite Mountain range, though most common patterns were groupings of populations along river drainages. While several cryptic species were identified, widespread groups likely representing single species still exist, and a phylogenetic component to broad distribution were noted.

Keywords: Evolution
Anurans
Advisor: Robert, Murphy
Measuring Semantic Distance using Distributional Profiles of Concepts

Semantic distance is a measure of how close or distant in meaning two units of language are. A large number of important natural language problems, including machine translation and word sense disambiguation, can be viewed as semantic distance problems. The two dominant approaches to estimating semantic distance are the WordNet-based semantic measures and the corpus-based distributional measures. In this thesis, I compare them, both qualitatively and quantitatively, and identify the limitations of each. This thesis argues that estimating semantic distance is essentially a property of concepts (rather than words) and that two concepts are semantically close if they occur in similar contexts. Instead of identifying the co-occurrence (distributional) profiles of words (distributional hypothesis), I argue that distributional profiles of concepts (DPCs) can be used to infer the semantic properties of concepts and indeed to estimate semantic distance more accurately. I propose a new hybrid approach to calculating semantic distance that combines corpus statistics and a published thesaurus (Macquarie Thesaurus). The algorithm determines estimates of the DPCs using the categories in the thesaurus as very coarse concepts and, notably, without requiring any sense-annotated data. Even though the use of only about 1000 concepts to represent the vocabulary of a language seems drastic, I show that the method achieves results better than the state-of-the-art in a number of natural language tasks. I show how cross-lingual DPCs can be created by combining text in one language with a thesaurus from another. Using these cross-lingual DPCs, we can solve problems in one, possibly resource-poor, language using a knowledge source from another, possibly resource-rich, language. I show that the approach is also useful in tasks that inherently involve two or more languages, such as machine translation and multilingual text summarization. The proposed approach is computationally inexpensive, it can estimate both semantic relatedness and semantic similarity, and it can be applied to all parts of speech. Extensive experiments on ranking word pairs as per semantic distance, real-word spelling correction, solving Reader's Digest word choice problems, determining word sense dominance, word sense disambiguation, and word translation show that the new approach is markedly superior to previous ones.

Keywords: Computational Linguistics
Natural Language Processing
Lexical semantics
semantic distance
distributional similarity
semantic similarity
semantic relatedness
word concept co-occurrence matrix
distributional profiles of concepts
thesaurus
corpus-based techniques
word senses
cross-lingual techniques
word sense dominance
word sense disambiguation
wordnet
Advisor: Hirst, Graeme
The Position of the Sammarinese Dialects in the Romagnol Linguistic Group

Although Italo-Romance varieties continue to be documented, classified, and analyzed by dialectologists, many are at risk of not being recorded thoroughly and systematically before their imminent extinction. While considerable attention has been devoted to the phonetics, phonology, morphosyntax, and lexicon of the more archetypal Romagnol dialects spoken in the Po Valley, dialectologists have largely overlooked peripheral Romagnol varieties such as Sammarinese. The present dissertation begins to fill this lacuna in Italian dialectology by providing an historical and synchronic study of Sammarinese phonology and morphology based on the examination of old and modern texts as well as copious oral data. The main purpose of the thesis is to delineate diatopic variation within the tiny Republic through comparative analysis, while also addressing the need for a more complete and precise definition of Sammarinese‘s position in the Romagnol linguistic group. In addition to confirming Sammarinese‘s status as a Borderline Romagnol variety, the dissertation offers evidence that Sammarinese is divided geographically into two main dialectal groups: Northeastern and Southwestern. The secondary intent of the thesis is to provide systematic, comprehensive, and phonetically precise documentation of the phonology and morphology of a moribund language. iii The dissertation consists of five chapters. The Introduction includes a brief linguistic history which relates diatopic variation to geopolitical factors. The first chapter also contributes an assessment of the status of scholarship dedicated to Sammarinese dialectology. Chapter 2 examines diachronic phonetics, emphasizing the dichotomy between the traits which link Southwestern Sammarinese to Borderline Romagnol and those which join Northeastern Sammarinese with the Romagnol varieties of the Po Valley. Chapter 3 treats synchronic phonetics and proposes a generative phonology which aims to identify the diasystem underlying phonetic variation within the Republic. Chapter 4 analyzes historical declensional morphology, underscoring diatopic variation in internal flexion configurations as further evidence of the division between Northeastern and Southwestern Sammarinese. Chapter 5 examines diachronic verb morphology. The dissertation concludes with an assessment of linguistic aspects meriting further research and analysis.

Keywords: Italian Dialectology
Romagnolo
Advisor: Danesi, Marcel
Fabrication and Characterization of Waveguides in Potassium Gadolinium Tungstate

This thesis describes the fabrication and characterization of waveguides in the nonlinear, Raman-active optical crystal potassium gadolinium tungstate (KGW). Ion implantation and femtosecond laser writing techniques are used for the first time to fabricate waveguides in this material. The light ion implanted waveguides using hydrogen ions showed unexpected refractive index increases in the damage regions of approximately 0.3% of the nominal refractive index values for three of the four polarization orientations, with only the highest refractive index polarization exhibiting a refractive index decrease of approximately 0.2%. Waveguides fabricated using high-energy carbon, oxygen and fluorine ion irradiations resulted in strongly confining waveguides with wide amorphous damage regions. Carbon ion irradiation of KGW showed the most promise, with sharp step-like waveguides with a maximum refractive index change of delta-n=0.2 with excellent preservation of the Raman properties in the waveguide core. Microreflectivity measurements on the carbon ion irradiated sample revealed unexpected intermittent refractive index changes in the core region, a feature not detected using standard characterization techniques found in the literature. The oxygen ion irradiation of KGW also generated strongly confining waveguides with a maximum refractive index change of delta-n=0.17, however the Raman performance was shown to be reduced to less than 50% in the waveguide cores. Fluorine ion irradiations of KGW resulted in amorphous regions fabricated in the surface regions, offering promise for masking techniques for creating two-dimensional structures. The waveguides written using femtosecond laser writing processes were used to write buried channel waveguides using compressive stresses to form the waveguide. These waveguides exhibited low-losses down to to 2.0 dB/cm in the telecommunications spectrum, with high coupling efficiency to SMF fiber, and excellent Raman properties in the waveguide core. These channel waveguides also successfully showed SRS generation into the 1.8-1.9 \mu m infrared region using a high power picosecond pump source in the telecommunications band. The use of the microreflectivity and micro-Raman spectroscopy measurement techniques were demonstrated to be valuable characterization tools for each of the fabrication methods.

Keywords: Waveguides
Raman
Microreflectivity
crystals
Advisor: Aitchison, J. Stewart
Nonparametric Bayesian Methods for Extracting Structure from Data

One desirable property of machine learning algorithms is the ability to balance the number of parameters in a model in accordance with the amount of available data. Incorporating nonparametric Bayesian priors into models is one approach of automatically adjusting model capacity to the amount of available data: with small datasets, models are less complex (require storing fewer parameters in memory), whereas with larger datasets, models are implicitly more complex (require storing more parameters in memory). Thus, nonparametric Bayesian priors satisfy frequentist intuitions about model complexity within a fully Bayesian framework. This thesis presents several novel machine learning models and applications that use nonparametric Bayesian priors. We introduce two novel models that use flat, Dirichlet process priors. The first is an infinite mixture of experts model, which builds a fully generative, joint density model of the input and output space. The second is a Bayesian biclustering model, which simultaneously organizes a data matrix into block-constant biclusters. The model capable of efficiently processing very large, sparse matrices, enabling cluster analysis on incomplete data matrices. We introduce binary matrix factorization, a novel matrix factorization model that, in contrast to classic factorization methods, such as singular value decomposition, decomposes a matrix using latent binary matrices. We describe two nonparametric Bayesian priors over tree structures. The first is an infinitely exchangeable generalization of the nested Chinese restaurant process that generates data-vectors at a single node in the tree. The second is a novel, finitely exchangeable prior generates trees by first partitioning data indices into groups and then by randomly assigning groups to a tree. We present two applications of the tree priors: the first automatically learns probabilistic stick-figure models of motion-capture data that recover plausible structure and are robust to missing marker data. The second learns hierarchical allocation models based on the latent Dirichlet allocation topic model for document corpora, where nodes in a topic-tree are latent ``super-topics", and nodes in a document-tree are latent categories. The thesis concludes with a summary of contributions, a discussion of the models and their limitations, and a brief outline of potential future research directions.

Keywords: 0800
Advisor: Roweis, Sam
Above and Below Ground Fungal Diversity in a Hemlock-dominated Forest Plot in Southern Ontario and the Phylogenetic Placement of a New Ascomycota Subphylum

The objective of this thesis was to assess the diversity and community structure of fungi in a forest plot in Ontario using a variety of field sampling and analytical methods. Three broad questions were addressed: 1) How do different measures affect the resulting view of fungal diversity? 2) Do fruiting bodies and soil rDNA sampling detect the same phylogenetic and ecological groups of Agaricomycotina? 3) Will additional rDNA sampling resolve the phylogenetic position of unclassified fungal sequences recovered from environmental sampling? Generally, richness, abundance, and phylogenetic diversity (PD) correspond and identify the same dominant fungal groups in the study site, although in different proportions. Clades with longer branch lengths tend to comprise a larger proportion of diversity when assessed using PD. Three phylogenetic-based comparisons were found to be variable in their ability to detect significant differences. Generally, the Unifrac significance measure (Lozupone et al., 2006) is the most conservative, followed by the P-test (Martin, 2002), and Libshuff library comparison (Singleton et al., 2001) with our dataset. Fruiting body collections and rDNA sampling recover largely different assemblages of fungi at the species level; however, both methods identify the same taxonomic groups at the genus-order level as well as ectomycorrhizal fungi as the dominant functional type of Agaricomycotina. This work also shows that the Soil Clone Group I (SCGI) clade is widespread in soils of diverse origins and represents a novel subphylum of Ascomycota.

Keywords: mycology
fungi
basidiomycota
ascomycota
soil
phylogenetics
Advisor: Moncalvo, Jean-Marc
Acute Care Nurse Practitioners', Physicians' and Staff Nurses' Relationships with Patients: A Descriptive, Comparative Study

Acute care nurse practitioners (ACNPs) are a new addition to the Canadian health care system, having been introduced in the Canadian health care system in the late 1980s. While some authors have suggested that nurse practitioners offer “something special” to patient care, no evidence to date has substantiated this claim. The findings of this grounded theory study offer a theory (Acute Care Health Professional-Patient Relationship (ACHPPR) Theory) to describe how three types of health care professionals establish relationships with patients in acute care settings (Figure 7). This qualitative study explored relationships that ACNPs, physicians and staff nurses establish with patients in a large urban multi-site university-affiliated hospital. Six quartets (patient, ACNP, physician, staff nurse) were recruited and interviews, using a semi-structured guide were audio-taped and subsequently transcribed verbatim. Each type of relationship was found to have a unique focus; ACNPs focus on making connections with patients, physicians focus on managing patients’ diseases and staff nurses focus on meeting patients’ needs. In order to establish relationships with patients, readiness conditions must be met. Health professionals use strategies to influence the achievement of readiness conditions as well as to move forward with relationship development. Each type of relationship varies in the range of potential intensity that can be achieved, which is influenced by various dimensions. Relational intensity ranges from the uncommon clinical relationship, which focuses on the patient’s disease, through the more typical professional relationship characterized by a comfortable rapport and then finally to the most relationally intense, but rare, personal relationship. If a relationship reaches professional or personal levels of relational intensity, relational products become evident. When comparing these three health professional-patient relationships, similarities and differences have been identified. Analysis of patient interviews yielded themes that substantiate the ACHPPR theory. The ACHPPR theory offers a beginning understanding of the complementary nature of three types of health professional-patient relationships in the acute care setting and has the potential to influence practice, education, theory development and future research related to ACNP-patient relationships.

Keywords: Interpersonal Relations
Professional-Patient Relationships
Nurse Practitioners
Advanced Nursing Practice
Acute Care Nurse Practitioners
Advisor: Pringle, Dorothy