VictorJuiz/thesis huggingface dataset:
Aristotle's Case for Perceptual Knowledge
Keywords: Aristotle
cognition
discrimination
knowledge
perception
realism

Sense experience, naïvely conceived, is a way of knowing perceptible properties: the colors, sounds, smells, flavors, and textures in our perceptual environment. So conceived, ordinary experience presents the perceiver with the essential nature of a property like Sky Blue or Middle C, such that how the property appears in experience is identical to how it essentially is. In antiquity, as today, it was controversial whether sense experience could meet the conditions for knowledge implicit in this naïve conception. Aristotle was a partisan in this debate, but his position is poorly understood. This dissertation examines how Aristotle’s perceptual psychology responds to ancient challenges to the naïve conception, and so articulates his defense of perceptual knowledge. Aristotle’s defense relies on an ontology of “perceptual qualities”—a core class of perceptible properties—according to which those qualities, despite having a perceiver-independent essence rooted in the physics of causation and affection, nevertheless can be present in experience as they essentially are. Chapter 1 defends this realist and objectivist reading against competing interpretations, which overlook a crucial distinction between perceptual qualities and perceptual objects. Chapter 2 presents Aristotle’s ontology as a physicalism that uncharacteristically allows for perceptual qualities to appear in experience as they essentially are. This ontology informs Aristotle’s account of the psychological conditions under which perceivers actually are presented with the essence of perceptual qualities. The locus of this account is an obscure passage where Aristotle purports to show that the senses “discriminate” perceptual qualities because the senses are “mean states” (An. 2.11, 424a5–7). Chapter 3 develops a comprehensive interpretation of the sensory mean state, which Chapter 4 uses to elucidate Aristotle’s argument for sensory discrimination. Sensory discrimination turns out to be a process in which the essence of a perceptual quality comes to be present in the affection it produces in a perceiver. For Aristotle, this shows that sense perception meets a condition for knowledge that his predecessors, including Plato, thought it could not meet. For in his view, but not in theirs, sense experience shares in both the truth and the essence of the qualities it perceives.
Poles Apart: The Debates on Religious Conversion in Post-independence India
Keywords: Christianity
Conversion
Hinduism
Legislation
Religion

This dissertation is an historical analysis of the ideological and religious debates over conversion to Christianity in India since its Independence in 1947. In particular, the study focuses on how these debates have played out within various forms of proposed and enacted anti-conversion legislation at the state and federal levels of government. The study identifies the key poles of the conversion debate, first set forth in Indiaâ s Constituent Assembly Debates, and which have remained remarkably uniform through 70 years of legislation, rhetoric, and scholarship. Chapter One situates the study within the context of existing scholarship on both conversion and Christianity in India, with a focus on emerging scholarly views of the manifold ways in which conversion can be defined. Chapter Two examines India as a secular nation and attempts to identify the status of religious minorities within a conceptual space which, while secular, reflects a predominantly Hindu worldview. Chapters Three, Four, and Five provide an extensive primary source analysis of the conversion debates preceding the patriation of the Indian Constitution, government reports, High Court rulings, and legislation proposed and enacted between 1947 and 1981. Chapter Six examines a second tranche of anti-conversion legislation enacted at the state level between 2002 and 2008, following the rise to power of the Hindu nationalist political parties at various levels of government in India. Chapter Seven examines contemporary expressions of the debate over religious conversion in India, with a focus on court challenges to existing anti-conversion legislation. Chapter Eight concludes the study, arguing that what is at stake for India as a secular state with constitutional protections for freedom of religion, is how both conversionâ s critics and proponents understand the diversity of motivations for converting, and how this knowledge is applied to ensure religious freedom for all of Indiaâ s citizens. Without understanding the motivation which underlie the debate, conversion will remain a contested and at times violently contested issue.
Stress Response Pathways Regulate Drug Resistance and Morphogenesis in the Human Fungal Pathogen Candida albicans
Keywords: Antifungal drug
Candida albicans
Drug resistance
Drug tolerance
Morphogenesis
Stress response

The dimorphic yeast Candida albicans is a leading causative agent of fungal infections in humans. Critical to C. albicans pathogenesis is its ability to transition between yeast and filamentous forms. Currently, a major clinical problem is the frequent emergence of resistance to existing antifungal drugs. Development of new antifungal agents remains a difficult process, partly due to the conservation of many potential therapeutic targets between C. albicans and humans. Moreover, stress responses in C. albicans enhance antifungal tolerance and enable drug resistance. Therefore, tactical targeting of specific stress response pathways that regulate drug resistance and morphogenesis in combination with known antifungal agents may provide a viable strategy to enhance the efficacy of antifungals and suppress the emergence of antifungal drug resistance. My doctoral research focuses on two cellular stress response pathways that are essential for drug resistance and the morphological transition in C. albicans. First, I uncover the regulatory circuitry through which the transcription factor Cas5 mediates cell wall stress responses, and establish Cas5 as a novel regulator of resistance to the echinocandin caspofungin. This represents the first example of transcriptional regulation as a mechanism of echinocandin resistance. Second, I reveal a novel and essential role for the protein kinase Pkc1 in regulating morphogenesis of C. albicans. I demonstrate that Pkc1 functions downstream of Rho1 in a signaling pathway that operates in parallel with the Ras1-PKA pathway. This is only the second pathway identified in C. albicans that has the capacity to integrate multiple filament-inducing cues and transduce the signals necessary for the transition from yeast to filamentous growth. Together, this research highlights the central role of cellular stress circuitry in drug resistance and morphogenesis, and uncovers attractive targets for the development of novel antifungal drugs, suggesting new avenues for combination therapies with current antifungal agents.
On-chip Manipulation and Sorting of Cancer Cells for Next-generation Diagnostic Technologies
Keywords: Chemotaxis
Circulating tumor cells
Metastasis
Microfluidics
Sorting

Cancer is a leading cause of death and disability. Early detection can significantly improve long-term survival in cancer patients. The advent of point-of-care technologies, which are typically based on lab-on-chip tools, enables convenient and real-time healthcare at or near the patient bedside. Development of point-of-care cancer testing can keep the advantages of, but overcome the high cost of, existing expensive genetic analysis methods. It can do so while providing the results promptly to physicians as they seek to customize and improve disease treatment. The central aim of this thesis is to develop new strategies to detect cancer prior to the spread of cancer cells to the distant organs. Metastasis relies on the release of migratory cancer cells, and is responsible for as much as 90% of cancer associated mortality. The factors that determine the invasiveness of these circulating cells remain poorly defined, and it is difficult to distinguish cancer cells having high versus low metastatic potential. New technologies are required that sort heterogeneous cancer cells into relevant subpopulations, and profile thereby small numbers of cells according to their phenotypes. Herein we describe a powerful new capability for the monitoring of cancer progression. We developed a novel fluidic chip that selectively isolates rare cancer cells that exhibit different levels of phenotypic surface markers. We show that the device successfully profiles the surface expression of very small numbers of cells; and it accomplishes this directly from whole blood. We couple the surface marker profiling approach with a migration platform with single cell resolution: this allows us to characterize more deeply, still on-chip, the biological behavior of invasive cancer cells. We deploy these new techniques to reveal the dynamic phenotypes of these rare cells. We prototype the system and prove it out using samples of unprocessed blood from mice. We characterize the samples as a function of tumor growth and aggressiveness and prove that the new profiling technology provides powerful and relevant information that correlates with tumor stage and aggressiveness. The strategies presented offer to guide the development of sensitive and specific approaches for cancer diagnosis that provide new information not available using prior methods.
Early Genomic Events Associated with Dissemination of Breast Cancer Cells
Keywords: Breast Cancer
Calcium Channels in Cancer
Circulating tumour cells
Genomic signatures
Metastasis
Tumour Heterogeneity

Deaths from breast cancer are due to metastases that are resistant to conventional therapy. In metastasis, tumour cells disseminate early on from the primary tumour into the blood or lymphatic system, and travel to distant organs, developing tumours at these new sites. The study of different cancer cells that make up a breast tumour, particularly cells that preferentially disseminate will help reveal how breast cancers progress, resist therapy, and metastasize. My goal was to characterize the early genomic alterations in breast cancer leading to dissemination. From our studies on sentinel lymph nodes, the first nodes that receive drainage from primary breast tumours, we found that chromosomal region 17q24, when gained in primary tumours, is strongly associated with lymphatic dissemination. I have characterized a calcium channel gene, CACNG4, within this region, and show that it increases metastatic propensity of breast cancer cells. It modulates intracellular calcium levels and affects the binding kinetics of channel antagonists, making it an appealing candidate for manipulating calcium channels in breast cancer. I have also identified genomic regions associated with hematological dissemination via circulating tumours cells (CTCs). CTCs have prognostic value in breast cancer, showing heterogeneity and dynamic evolution during cancer progression, with important therapeutic implications. Using immunomagnetic cell sorting and high-resolution copy number analysis, 90 regions recurrently gained in CTCs from breast cancer were identified, the majority of which were on chromosome 19. From these regions, 151 genes were validated in an in vivo chick embryo model, out of which 6 increased the metastatic potential of breast cancer cells. Concomitantly 8 regions were selected, and using multi-spectral fluorescent in situ hybridization, their distribution in tumours was examined. I have shown that cells with CTC-like region gains are present at low proportions in primary tumours with high intra-tumour heterogeneity. Notably, tumour cells with higher genomic imbalances within these regions are specifically selected for in metastases and recurrences, post-treatment. The results presented herein implicate genomic alterations, gained heterogeneously within breast cancer cells that are associated with metastasis. If targeted before they leave the primary tumour, dissemination itself could be blocked.
Identification of Factors Involved in the DNA Repair Phase of B Cell Class Switch Recombination
Keywords: Antibodies
Cancer
CRISPR
DNA Repair
RNA Interference

B cells undergo class switch recombination (CSR) in order to modify their antibody isotypes during an immune response. Different antibody isotypes convey unique immune functions, predominate in different tissue environments, and are responsible for clearance of a distinct array of pathogens. CSR requires the timely repair of DNA double-stranded breaks (DSBs) generated at the immunoglobulin locus that emerge from self-inflicted genetic lesions introduced by the enzyme activation-induced cytidine deaminase (AID). Researchers have taken advantage of the programmed DSBs generated during CSR to make significant conceptual insights into the mechanisms of DSB sensing, the DNA damage response (DDR), and the resolution of DSBs through various recombination or end joining pathways. Nonetheless, our comprehension of the DSB repair phase of CSR remains incomplete, with significant knowledge gaps in understanding which factors are recruited to DSBs, how they assemble in the context of various post-translational modifications, and how their dynamic functions influence the choice between different downstream repair pathways. We completed a genome-wide RNA interference screen in the murine B cell line CH12F3-2 with the goal of identifying novel factors involved in the repair phase of CSR. With this system, we selected three candidates, Kin, Eny2, and Usp22, as factors for further investigation. We confirm that Kin is critical for optimal CSR and is required for the functionality of multiple DSB repair pathways. Moreover, we demonstrate that Eny2 and Usp22, both members of the H2B deubiquitination module of the SAGA complex, maintain CSR by regulating the expression of the ÎłH2AX histone mark, a key intermediate in the DNA damage response. These findings uncover new ground for our growing understanding of cell-ubiquitous DSB repair, with implications in cancer, immunity, and aging.
Women and Hormones in Tibetan Medical Literature
Keywords: hormones
TIbetan Buddhism
TIbetan medicine

This dissertation examines a contemporary genre of Tibetan medical writings that seek to integrate Tibetan medical and biomedical notions of “hormones” in the reproductive bodies of women. The analytical lens of ‘gender’ plays a significant role in this dissertation, specifically the ways in which medical and Buddhist language and literature surrounding the Tibetan integration of biomedical notions of hormones deeply implicates modern-day Tibetan national, ethnic, and religious identities. This dissertation provides overviews and analyses of a selection of recently published Tibetan medical works that research methods to integrate and articulate biomedical notions of ‘hormones’ into the Tibetan medical system. These works include book-length commentaries, medical journal articles, book chapters, and home reference books that focus on women’s health. This dissertation analyzes the relationship between establishing medical authority with the practice of textual research in present-day Tibetan medical writing in ‘Chinese Tibet,’ and how ‘hormones’ are the central point of intersection and integration between the Tibetan medical and biomedical systems. Many present-day Tibetan medical authors turn to Buddhist thought, and specifically the texts and language of Tantra, to explicate and articulate the Tibetan understanding of hormones. In their research into the authoritative and classical texts of their traditions, the majority of the authors discussed within this dissertation argue that it can be definitively established that the classical Indo-Tibetan medical and Buddhist writers and experts ‘knew’ about the very subtle substances circulating throughout the body that are today known in biomedicine as “hormones.”
The Built Environment: Spatial and Social Interaction at Pot Creek Pueblo, New Mexico
Keywords: 3D computer modelling
3D visual analysis
community interaction
settlement archaeology
space
vision

This dissertation develops a new archaeological approach for analysing social interaction through the built environment of ancient communities by amalgamating various theoretical approaches, three-dimensional computer modelling, and spatial analysis. I apply this approach to Pot Creek Pueblo, New Mexico, which grew from several individual ‘unit pueblos’ into a Period III village with large, multi-storied buildings, during the period A. D. 1270 - 1320. I explain how spatial environments arranged inhabitants’ movements and social encounters, while creating and reinforcing social organizational structures. Previous research on architecture at Pot Creek has primarily relied on functional and ritual perspectives; in contrast, I delve into ways that the inhabitants of Pot Creek used buildings and site development to produce, maintain, and reproduce social structures. To understand these issues, I use theories from environment-behaviour studies and urban planning with an emphasis on non-verbal, visual communication in spatial settings. I examine visual pathways between plazas during the morphological development of the village. The findings show that the buildings of Pot Creek were carefully constructed and situated to manipulate visual and social interaction. From the earliest occupation the plazas did not permit intervisibility with one another, and developed an increasing sense of enclosure throughout the occupation sequence. Private and public spaces were carefully orchestrated allowing differing levels of social interaction. I also examine visual taskscapes surrounding corn grinding to understand how the built environment structured the social interaction of teaching and learning. I found that distinct differences in the built environment brought to light different patterns of social interaction for female corn grinders. Participation and learning would have varied widely between enclosed grinding rooms and open-sided ramadas where corn meal production took place. The results offer insight into how people in the past socially interacted within the confines of their spatial environment, as built environments provide non-verbal cues to structure behaviour, even during mundane tasks such as grinding corn. This research has allowed me to think and see the spatial environment in a humanized way, to ‘see’ from a perspective of past village occupants and could be applied to varying site scales and geographic regions.
Fear of Cancer Recurrence Among Survivors of Adult Cancers
Keywords: Cancer Survivorship
Fear of Cancer Recurrence
Psychosocial Oncology

Purpose: Fear of Cancer Recurrence (FCR) is a common concern for which cancer survivors want professional help to cope. Understanding the prevalence, predictors and mediators of FCR is important to facilitate the identification of those at-risk for clinically-significant FCR in order to expediently refer them into appropriate interventions. To clarify the empirical gaps which would be useful in this regard, the objectives of this study were: 1) to assess the prevalence of FCR; 2) to examine the relationships among predictors of FCR; and 3) examine the relationships among mediators of FCR. Methods: Survivors attending a cancer survivorship clinic were invited to participate in this cross-sectional, mixed mode survey study. Participants completed standardized assessments of FCR, Self-Esteem, Personality, Generalized Expectancies, Illness Representations, and Coping Styles, in addition to a demographic form. Clinical and treatment information was extracted from hospital charts. SPSS was used to conduct descriptive statistics to address objective 1, and Mplus was used to conduct a structural equation modeling analysis to examine predictors and mediators of FCR. Results: One-thousand two participants completed the survey. The mean age was 61.1 years and most were female (85.2%). The mean time since diagnosis was 9.1 years (range 1-36 years) and most were diagnosed with breast cancer (66.2%). Nearly fifty-nine percent of the sample had clinically-significant levels of FCR. Age, sex, symptom burden, associations with cancer, self-esteem and optimism had direct effects on FCR. The Timeline (acute/chronic) and Emotional Representation components of an Illness Representation, and both Coping Styles, were found to mediate some of these relationships. Conclusions: This study found that a large percentage of survivors continued to experience clinically-significant FCR, even years after diagnosis. The identified predictors of FCR may be useful to identify those with higher FCR, while the identified mediators may have utility for intervention development and refinement.
Ambulatory Clinic Scheduling
Keywords: clinic scheduling
healthcare
integer programming

In this thesis we seek to fully explore the ambulatory clinic scheduling problem (CSP) and study the creation of ambulatory clinic schedules using mathematical models. We describe our experiences developing ambulatory clinic schedules for three healthcare facilities including the challenges we faced, lessons learned, and value provided to our partner organizations. Based on our experiences we identify and model the key elements of the CSP, providing a general model for future use. To solve our general clinic scheduling model we identify the problem in literature with the structure most similar to the CSP and consider solution approaches that may be adapted for the CSP. We adapt a solution approach for the multi-resource generalized assignment problem to the CSP based on insight gained through our practical experience. Our adaptations improve the solution approachâ s performance on the CSP. This thesis will establish the clinic scheduling problem as an important healthcare operations problem alongside other popular and well-studied healthcare scheduling problems such as personnel and operating room scheduling.