VictorJuiz/thesis huggingface dataset:
Gene Expression Changes in Rats with Diastolic Dysfunction Induced by Diabetes and Hypertension, and in Humans with Diastolic Heart Failure

Current therapies for heart failure are administered across a heterogeneous spectrum of disease etiology and phenotype. Standard treatments for systolic heart failure are not efficacious for patients with diastolic heart failure, raising the possibility that as of yet unidentified mechanisms are responsible for disease pathogenesis. We observed that diabetic rats treated with Angiotensin II infusion developed cardiac hypertrophy, fibrosis, and impaired diastolic function. Using a systems biology approach, we identified (a) changes in the cardiac transcriptome of rats in response to diabetes and hypertension; (b) the subset of genes that were simultaneously regulated in both the heart and whole blood of rats exposed to diabetes and hypertension; and (c) differentially expressed genes in whole blood of patients with diastolic heart failure compared to those with systolic heart failure and controls. In each experiment, we identified differential expression of functionally related groups of genes, suggesting coordinated regulation of multiple genes. Protein processing, extracellular matrix remodeling and inflammation were three of the dominant processes in cardiac tissue of diabetic hypertensive rats that were simultaneously regulated in whole blood. Extracellular matrix protein 1, transforming growth factor beta family members, and angiopoietin-like four were identified as part of a panel of extracellular matrix mediators that were coordinately regulated in both tissues. Gene expression profiles in blood of patients with diastolic heart failure allowed us to study networks and relationships of interactions that may not have been available from the study of single targets. A panel of eleven candidate markers was identified, including several that participate in cytoskeletal rearrangement or cell adhesion (plexin C1, transgelin 2, ninein, villin 2, and dock 2), and others involved in protein processing (ubiquitination factor E4B, myotubularin related protein 3, presenilin 1). These sets of experiments contribute to the literature regarding the myocardial effects of diabetes and hypertension and provide novel insight into the coordinated regulation of genes in the heart and blood in response to cardiovascular stress. The list of top candidate genes identified from the blood of patients with diastolic heart failure may have clinical utility as disease biomarkers.

Keywords: Gene expression
diastolic dysfunction
Advisor: Liu, Peter
Seeing the Proof: The Question of Contacting the Hidden Imam in Early Twelver Shīʿī Islam

The history of what has come to be known as Twelver Shīʿī Islam since the late 3rd/9th century is a history of attempts to deal with the abrupt loss of the Imam. According to the Imāmī/Twelver Shīʿa, the final Imam, known most famously as the Qāʾim and Mahdī, did not die like the Prophet Muḥammad and the previous eleven Imams but rather concealed himself (commonly referred to as the Imam’s ghayba or occultation) and continues to be physically alive on earth while waiting for the appointed time of his (re)appearance. A letter said to have been dictated by the Imam in the year 329/941 on the eve of what has come to be known as the period of the Greater Occultation declared anyone who claims to see him before his return a “lying impostor.” Based on a critical study of this letter and the earliest extant Shīʿī sources concerning the occultation and in particular the question of seeing and contacting the Hidden Imam, this dissertation will show that in the early years of the Greater Occultation, Shīʿī authorities maintained that seeing the Imam was no longer possible. This position, however, proved untenable to maintain before historical exigencies and the incessant longing for direct contact with the Imam. Almost a century after the start of the Greater Occultation, prominent scholars began to concede the possibility that some Shīʿa can see the Hidden Imam, thus foreshadowing a radical shift. A century later, accounts began to appear detailing encounters between the Imam and the most privileged of his votaries in a wakeful state. In the earliest accounts, the Imam is most often presented as a healer and miracle-worker. It is much later, after the Imam’s final letter had been negotiated, that the stories of encounters with him began to grow in number and become more embellished. While the Imam continues working miracles, in some of these later accounts, he also answers vexing legal or theological questions to prominent Shīʿī ulama, in essence providing the same direct knowledge to his de facto surrogates that is believed to have been suspended when the Greater Occultation began.

Advisor: Lawson, Todd
Genetic Investigation of MHC-independent Missing-self Recognition by NK Cells

NK cells are innate lymphocytes involved in the elimination of transformed, infected, stressed, antibody-coated and transplanted cells. The goal of this thesis, as well as the interest of our laboratory is to explore the MHC-independent “missing-self” branch of NK recognition, and more specifically, the NKR-P1B:Clr-b receptor-ligand system and its role in bone marrow transplantation. In the first results chapter, we generated hybridoma clones producing monoclonal antibodies against another inhibitory receptor in the Nkrp1 receptor family, NKR-P1G via the CELLISA assay. Our results demonstrate that CELLISA is a cost-effective, efficient, and high-throughput screening protocol, and the generation of the α-NKR-P1G 1H8 hybridoma clone enables characterization of the mouse Nkrp1-Clr receptor-ligand system via in vitro reporter cell and transfection approaches. Next, we show that the Nkrp1-Clr receptor-ligand system exhibits substantial allelic polymorphisms in NKR-P1B, NKR-P1C, and Clr-c loci between three common laboratory inbred mouse strains (C57BL/6, BALB/c and 129); however, no differential gene content has been observed in these loci in contrast to the Ly49 and MHC-I loci in mice. Furthermore, through the usage of BWZ reporter cell assays, we reveal several new cognate receptor-ligand pairs in addition to the previously reported NKR-P1B:Clr-b and NKR-P1F: Clr-g interactions; they are: NKR-P1F: Clr-c; NKR-P1F: Clr-d; NKF-P1G: Clr-d; NKR-P1G: Clr-f; NKR-P1G: Clr-g. In the final results chapter, we show that Clr-b–/– bone marrow cells are rejected by the recipients’ NKR-P1B+ NK cells. Importantly, through the usage of a 7-colour membrane labeling technique on the donor cells, we can simultaneously compare the rejection of Clr-b–/– grafts to WT cells and different variants of MHC-I-deficient bone marrow cells in a single animal. Up to 30-40% of Clr-b–/– bone marrow cells were rejected, which is similar to the rejection phenotype for H-2Db–/– bone marrow cells. Importantly, this rejection is reverted fully or partially (in B6 vs. Swiss recipients) in NK-depleted (total or NKR-P1B+ NK subset depleted) recipients. Collectively, these results extend our understanding of the Nkrp1-Clr receptor-ligand family by revealing additional Nkrp1-Clr receptor-ligand pairs; and that the missing-self recognition of Clr-b in vivo is instrumental in determining the prognosis of bone marrow transplantation.

Keywords: NK Cells
Bone Marrow Transplantation
Cancer
Clr-b
Advisor: Carlyle, James R.
The Client's and Therapist's Vocal Qualities in CBT and PE-EFT for Depression

The psychotherapy client’s vocal quality indicates the quality of and shifts in the client’s engagement in treatment. In contrast, the therapist’s vocal quality is a treatment intervention, either facilitating or hindering the client’s progress. The Client Vocal Quality (CVQ) and Therapist Vocal Quality (TVQ) measures (Rice & Kerr, 1986) were applied to responses in the middle 20 minutes of low and high change sessions for 61 clients who received either cognitive behavioural therapy (CBT) or process-experiential emotion focused therapy (PE-EFT) for depression (Watson, Gordon, Stermac, Kalogerakos, & Steckley, 2003). Sessions were selected using the Client Task Specific Change Measure-Revised (CTSC-R; Watson, Greenberg, Rice, & Gordon, 1996). Outcome measures included the Beck Depression Inventory, Dysfunctional Attitude Scale, Global Severity Index of the Symptom Checklist-90-Revised, Inventory of Interpersonal Problems, Problem-Focused Style of Coping Scale, and Rosenberg Self-Esteem Scale. The CVQ categories differentiated between treatment types, with PE-EFT clients expressing a significantly higher proportion of Emotional vocal quality and CBT clients expressing a significantly higher proportion of Externalizing vocal quality. There was no difference between the treatment types for Focused or Limited vocal quality. The CVQ categories predicted outcome. This relationship was particularly evident in the session in which clients first reported moderate to high change on the CTSC-R. The combination of Emotional and Focused categories was a stronger predictor than either category alone. In contrast, a higher proportion of Externalizing vocal quality predicted worse scores. In terms of Therapist Vocal Style, PE-EFT therapists spoke predominantly in the Softened-Irregular Vocal Style, while CBT therapists spoke predominantly in the Natural-Definite Vocal Style. Therapists’ use of a Softened-Irregular Vocal Style, compared with a Natural-Definite Vocal Style, was associated with the client’s report, at the end of therapy, that he/she felt less easily exploited by others and had a greater ability to assert interpersonal boundaries without fear of offending others. Limitations of the study are discussed.

Keywords: vocal quality
Client Vocal Quality
Therapist Vocal Quality
psychotherapy processes
CBT
Emotion Focused Therapy
Process Experiential Therapy
Advisor: Watson, Jeanne
The Struggle for North Africa between Almohads, Ayyubids, and Banū Ghāniya (Late Twelfth to Early Thirteenth Centuries A.D.)

This thesis is concerned with the invasion of the Almohad Empire by the Banū Ghāniya of Majorca and the Ayyubid amir Sharaf al-Dīn Qarāqūsh in the late twelfth and early thirteenth centuries A.D. This long and destructive conflict, which sapped the strength of the Almohad state in North Africa, has received little attention from modern scholars, particularly in the west. It is our aim to contextualize the revolt of the Banū Ghāniya and Qarāqūsh’s expeditions within the wider African and Mediterranean worlds. In particular, we will shed light on the economic background of the great power rivalries that affected North Africa during this period. The Banū Ghāniya were descendants of the Almoravids who established a principality in the Balearic Islands after the fall of the Almoravid state in the mid-twelfth century. In 1184 they invaded North Africa and fought against the Almohads in a struggle which lasted until the 1230s and ranged from Tripoli to Sijilmāsa under the amirs ʿAlī (1184-1187) and Yaḥyā b. Ghāniya (1188-1235?). The arrival of the Banū Ghāniya in North Africa coincided with the conquest of Almohad Ifrīqiya (Tunisia) by the Ayyubid amir Sharaf al-Dīn Qarāqūsh. For several years Ayyubid forces fought side by side with the Banū Ghāniya and various Arab tribes against the Almohads until Ṣalāḥ al-Dīn made peace with the latter in 1190. The tenacious resistance of the Banū Ghāniya and their allies, though ultimately unsuccessful, put an end to Almohad dreams of an empire embracing all of northwest Africa and forced them to eventually relinquish their hold on Ifrīqiya and the Central Maghrib which passed under the rule of the local Hafsid and Zayyanid dynasties in the first half of the thirteenth century.

Keywords: History
Medieval
North Africa
Maghrib
Egypt
Mediterranean
Sahara
Almohads
Ayyubids
Banu Ghaniya
Fatimids
Qaraqush
Advisor: Northrup, Linda
Hybrid SC-Inductive Based Topologies for Low-volume High-efficiency Switched-mode Power Supplies

Switched-mode power supplies (SMPS) are widely used as the voltage or current regulators for electronic devices. The most commonly used SMPS are inductive converters based on conventional buck and boost converter topologies due to their simplicity and relatively high power density and efficiency. However, in applications with large voltage difference between their inputs and outputs, these converters suffer from excessive losses and increased volume due to more demanding filtering and also cooling requirements. Therefore strong and ever increasing demands for developing smaller and more efficient SMPS with high conversion ratios exist.In this work two new converter topologies suitable for applications with large input-to-output voltage difference are introduced for both input voltage step-down and step-up in two different types of applications, i.e. for dc-dc converters and rectifiers with power factor correction. These converters are developed based on the concept of merging Switched-capacitor (SC) and inductive based converter stages by means of newly emerged digital controllers, improving efficiency and reducing the overall volume of the converter. Hence, the benefits of high power density SC-based converters are exploited and at the same time the input-to-output voltage ratio for the inductive stage is reduced improving its power density and efficiency. Compared to two-stage solutions, by merging SC and inductive based stages, switches between two stages are shared, reducing conduction losses, intermediate/flying capacitors are eliminated and controllers are unified.The buck-based, voltage step-down solution combines a capacitive divider and an interleaved buck to reduce the volume of multi-phase step-down converters. Experimental results obtained with a 7V-to-1V, 10A, 1 MHz prototype demonstrate that the merged capacitor converter has 15% smaller inductor, 13% smaller output capacitor, up to 35% lower power losses and 15% shorter settling time after transients.In the boost-based voltage step-up solution, the improvements are achieved by replacing the output capacitor of the boost converter with a non-symmetric active capacitive divider, with a 2:1 division ratio, effectively providing four-level converter behavior. Experimental results obtained with a 350 W, 200 kHz, universal input voltage (85Vrms - 265Vrms) PFC prototype demonstrate 66% reduction of boost converter inductor and up to 10% improvement of efficiency.

Keywords: Power electronics
power supply
SMPS
switched capacitor
switched mode
Advisor: Prodic, Aleksandar
Unique and Interdependent Roles of Lck and Fyn in TcR Signalling

It is not known whether or how the functions of Lck and Fyn are coordinated during TcR-medicated T cell activation. Our laboratory has previously demonstrated that lipid rafts (LR) function to segregate Lck and Fyn and are responsible for temporal and spatial regulation of their enzymatic activities. Specifically, Fyn localizes to LR, and the majority of Lck partitions to soluble membrane fractions. Co-aggregation of TcR and CD4 results in Lck activation outside LR, followed by its translocation into LR and the activation of LR-resident Fyn. This study, firstly, illustrates that ectopic expression of Lck variants in fibroblasts co-infected with wild type Fyn results in the formation of Lck-Fyn complexes and activation of LR-resident Fyn. Mutational analyses identified two domains of Lck critical for Lck-Fyn complex formation: (i) the active kinase domain of Lck, and (ii) the C-terminal QPQP sequence of Lck which functions as a cis-acting structural element required for partitioning of Lck to LR in fibroblasts and T cell clones. Secondly, the study shows that Fyn-/- mice succumb to influenza infections due to the lack of T cell expansion and homing to the lung. Moreover, using a preclinical model of colitis, the impaired expansion of inducer Fyn-/- T cells and the onset of disease is due to impaired IL-2 production in the absence of Fyn. Next, by means of an adenovirus-based vector system in combination with mice transgenic for the human coxsackie/adenoviral receptor (CAR), the study highlights that, both the impaired IL-2 production in vitro, and the onset of disease in vivo are rescued upon reintroduction of Fyn into Fyn-/- T cells. Lastly, the study demonstrates, using Lck-/- primary T cells, that both Fyn activation and the ensuing IL-2 production are Lck dependent. The results reconcile the obligatory and interconnected roles of both Lck and Fyn in T cell signalling.

Keywords: Immunology
Advisor: Julius, Michael
Informing Physician Communication with Children Regarding Weight: Family Perceptions and Motivational Interviewing Tools

The goal of this research was to understand perceptions of children with obesity (study 1), their parents (study 2), and physicians (study 3) regarding weight-related communication in primary care through qualitative methods. These perceptions informed a randomized clinical trial (Motivational Interviewing (MI) vs. education) (study 4) addressing physician identification and communication about weight in primary care. Studies 1, 2, and 3: Separate focus groups and individual qualitative interviews with 35 children with obesity (5-17 years of age), their 42 parents and 12 primary care physicians were completed. The aims were to understand how the three participants of weight-related discussions in primary care perceived communication and obesity management. Data analysis was completed using the fundamental descriptive method for content analysis. Children identified factors perceived to hinder and promote positive attitudes towards weight-related behaviour change. Parents identified familial factors and feelings, perceived physician practices (parent-physician interactions and child-physician interactions), and recommendations from parents. Physicians identified barriers to weight management, how they cope and their needs for addressing weight with children. Study 4: The aim of this randomized controlled trial of MI vs. education-based training for primary care physicians was to improve the identification of obesity and communication with children with obesity, and to determine the efficacy of the MI training on MI skill retention. Outcomes included changes in rates of BMI calculating, tracking and identification of obesity, change and retention of MI scores in those randomized to the MI group. Factors associated with primary outcomes were also identified. This study indicated that primary care physicians are a difficult group to engage as subjects for training interventions. Collective physician training in management of obesity is effective at improving BMI calculation and obesity identification rates. The MI training curriculum can be applied in a brief session and group format and results indicate adoption and maintenance of MI scores on empathy, collaboration and autonomy support. The studies in this thesis identify areas where communication about weight in primary care can be targeted. They highlight a potential for MI training and adoption of technique as means of improving counseling confidence. It also identifies challenges in physician enrollment and participation in trainings.

Keywords: childhood obesity
physician education
Advisor: McCrindle, Brian
Measurement Properties of the Whiplash Disability Questionnaire in Acute Whiplash-associated Disorders

Whiplash-associated disorders (WAD) include physical and psychological symptoms that may lead to disability. However, measuring disability following whiplash injuries is challenging because we lack valid and reliable measurement tools. The assessment of WAD-related disability relies on self-reported instruments that are specific to neck pain and do not comprehensively target the constructs associated with WAD-related disability. Designing new tools and evaluating their measurement properties is challenging because of the apparent inconsistencies in the theoretical frameworks (psychometrics and clinimetrics) used in instrument development and in reliability, validity and responsiveness evaluation. A scoping review design was used to develop a conceptual theory on the difference between clinimetrics and psychometrics in order to provide recommendations for future application. The scoping review of psychometric and clinimetric methods suggested that the two frameworks are not as divergent as reflected in the current protracted debates. Content analysis revealed that differences only exist in the scope of what is measured and in instrument development methods with no operational differences in the testing phases. Based on content analysis, I developed a new framework that bridges the two measurement schools with an overlapping informed zone between them. I designed a cohort study of 130 participants with acute WAD to assess the measurement properties of the Whiplash Disability Questionnaire (WDQ). The WDQ is a recently developed instrument designed to capture the broad construct of WAD-related disability. The WDQ measurement properties were determined in adults with WAD recruited within 21 days of their collision. My study indicates that the WDQ and its subscales are reliable and valid for clinical and research use. The WDQ can demonstrate change over time as a single scale or as the daily activities subscale. However, WDQ users should be aware of its measurement error when demonstrating change over time. Furthermore, the emotional subscale should not be used alone to demonstrate change over six weeks because it was not responsive. My thesis proposes a unified framework for studying the measurement properties of assessment tools used in clinical practice. I also demonstrated that the WDQ possesses the necessary properties to be used in patients with acute WAD.

Keywords: Measurement
Disability
Whiplash Injuries
Clinimetrics
Psychometrics
Reliability
Validity
Self-report Instrument
Advisor: té, Pierre Cô