VictorJuiz/thesis huggingface dataset:
Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate
Keywords: Stem cell bioengineering
hematopoiesis

Umbilical cord blood (UCB) cells fill a clinical need for hematopoietic stem and progenitor cell (HSPC) transplantation, and the ex vivo expansion of these cells provides an approach to increase their clinical relevance. Ex vivo HSPC expansion has been limited by a poor understanding of the interplay between stem cell autonomous and feedback mediated regulators. We hypothesized that developing strategies to modulate the HSPC microenvironment would enable enhanced expansion of these cells and a greater insight into the underlying biologic mechanisms. We developed a system for the optimized delivery of the transcription factor HOXB4 to human hematopoietic culture and revealed new insights into the context-dependent potentials and limitations of HOXB4. We investigated approaches for the global reduction of inhibitory feedback signaling and developed a fed-batch system that minimizes endogenously produced factors to create a more supportive environment for HSPC self-renewal. This strategy led to an 11-fold expansion of long-term repopulating HSCs in a clinically relevant bioreactor, producing a novel system for ex vivo expansion and generating a platform to assess HSPC enhancing factors. By combining the fed-batch system with the Notch Delta-1 ligand (DL1), we identified a mechanism whereby DL1 initiated a conversion from IL-6 cis-signaling to trans-signaling, resulting in the modulation of mature cell population production. This demonstrated the impact of cell lineage skewing on microenvironment regulation and the expansion of HSPCs. This work demonstrates how cell-cell interactions and feedback mediated signaling are critical regulators of HSPCs and the manipulation of these regulators can be used both to engineer HSPC expansion processes and to identify novel mechanisms within the hematopoietic system. This provides an important step towards the development of robust methods for the ex vivo expansion of UCB-derived cells and the ultimate goal of achieving cures in hematologic disease.
Death in a New Key: The Christian Turn of Roman Sarcophagi
Keywords: sarcophagi
Christian sarcophagi
early Christian art
funerary art
Jonah
traditio legis
late antiquity
refrigerium interim
reception
visibility
Christian number

Christian sarcophagi were produced in Rome during a long fourth century for a narrow audience. Their iconography marks a discontinuity in a centuries-old medium, a turn away from pagan and profane themes towards biblical narratives and Christian ideas. Following their patrons and viewers, these sarcophagi “converted” to a new religion and visually expressed its novel conception of death. This dissertation approaches these monuments as autonomous historical documents that merit examination on their own terms, which is not to deny the importance of social, economic, religious or artistic developments. Some of these extrinsic elements of context are addressed in the initial chapters. In particular, inferences are drawn concerning the cohort of individuals who bought, occupied and saw these sarcophagi based on estimates of cost and the Roman income distribution. Visibility, conditions of access and the circumstances of reception are also examined. Following these contextual considerations, the study focuses on two distinct and chronologically separated groups of Christian sarcophagi. The first consists of monuments with the Jonah theme, the single most popular form in the period before 350 CE. Jonah sarcophagi are representative of the widespread use of scriptural symbolic narrative, combining Old and New Testament allusions with other potential associations. The second group are sarcophagi displaying the so-called traditio legis (a modern Latinism), an important example of the late-century “conceptual” forms that allude to religious tenets without any specific scriptural anchor. This complex and controversial form of representation suggests a composite design, a conflation of images into a single form. Through a close reading of both the Jonah and traditio legis sarcophagi, the discussion elucidates various facets of reception and a range of over-determined and alternative meanings. The conclusion considers how the fourth-century Roman sarcophagi contributed to the construction of a Christian imaginaire of Christian death among their viewers.
Negotiating Pakistan: A Genealogy of a Post-colonial Islamic State
Keywords: Colonialism
Islam
Islamic State
Pakistan
Post-colonial

This dissertation explores the possibilities of Islamic statehood in post-colonial Pakistan through the works of three figures involved in framing the idea of the Islamic state: W.C. Smith, Muhammad Asad, and Muhammad Munir. Each of these three thinkers owes their position and prestige to the dynamics of colonialism, either as one employed in colonial educational institutions and the western academic study of Islam (Smith), or one involved in the critique of empire (Asad), or one tasked with adjudicating the new post-colonial state and its relationship to Islam (Munir). Although their projects embraced to some extent an extension of the colonial state's hegemonic practices of domination and control, the state was seen by these thinkers as a space in which liberal values could be impregnated with Islamic authenticity. Each of them would find ready opponents amongst the `ulama and the Jama'at, who imagined the creation of Pakistan as an opportunity to return to a precolonial past. In exploring these stories, I aim to complicate the genealogy of the Islamic state idea as it was conceived in Pakistan and to provide a perspective from which to understand the ongoing struggles of the Pakistani state to come to terms with both its religious and secular heritage.
I testi della paura e dell'incubo
Keywords: Italian Cinema
Horror genre
1960-1980
Popular Cinema

Between 1960 and 1970 Italy undergoes a major anthropological change, triggered by the mass migration to the industrialized cities of the North from the rural areas that had been the cradle of an old and profoundly rooted culture. In this historical frame, the Italian film industry becomes the most powerful and successful in Europe, starting a period of dominance and unparalleled growth that lasted almost twenty years. Genre films represent the backbone of the industry, and horror films, even though not the majority in numeric terms, become a significant section of the Italian production; Italian horror films establish and define new trends for the genre, largely imitated and admired. The thesis analyzes and discusses these films against the broader background of the years spanning from 1960 to 1980. The most important theoretical issues concerning the subject of the research are dealt with in Chapter one, where intertextuality is viewed as the most stimulating characteristic of the genre. Through the analysis of the Gothic tradition and the enumeration of several semantic elements linked to the genre, the thesis finds in the concepts of authorship and parody its essential critical tools for the following chapters. The evolution of the genre through the period 1960-1980 is examined in Chapter two. Films and directors are discussed not simply for the aesthetic value of their works, but mainly the for the contribution brought to the setting of the trends of the genre. This chapter examines also the influence of other media (the comic books and the television) on the process. The career of the two most important masters of the period, Mario Bava and Dario Argento, is explored and discussed in detail in Chapters three and four. The originality of their work marks the entire evolution of the genre. The Italian horror cinema cannot be conceived or thought of without the films made by Mario Bava and Dario Argento in the period examined by the research.
Facile Grown Native Oxide Based Passivation of Crystalline Silicon: A Novel Approach for Low-Temperature Synthesis of Silicon Photovoltaics
Keywords: Solar Cell
Crystalline Silicon
Amorphous Silicon
Passivation
Back contact
Photovoltaic
BACH
LIT
Native oxide
PECVD
Silicon nitride
Low temperature

Passivation of the crystalline silicon surface is central to the attainment of high-efficiency silicon solar cells and even more so as the silicon absorber is thinned. Moreover, the current predominantly high temperature processing of thin silicon wafers gives rise to defect migration-creation and thermal stresses in a typical multi-layered photovoltaic (PV) device. The development of a simple and effective low temperature passivation scheme would aid immensely in the synthesis of next generation low-cost high-efficiency thin silicon solar cells. This research proposes, investigates and demonstrates the efficacy of a novel low-temperature passivation scheme for crystalline silicon surface which consists of a facile grown native oxide (SiOx) layer and a silicon nitride (SiNx) over layer. A systematic experimental study of the interfacial passivation quality reveals that high quality surface passivation is obtained at a saturation native oxide thickness of ~10Å. The passivation quality is uniform over a large silicon surface with a surface recombination velocity (SRV) of 8 cm/s. Recombination modelling of the interface shows that the interfacial defect density diminishes with increasing native oxide thickness while the trapped charge density is essentially unchanged. In light of the new passivation scheme, this research investigates theoretically and experimentally a legacy photovoltaic cell concept, the Back Amorphous-Crystalline silicon Heterojunction (BACH) PV device, and proposes a novel PV cell concept - the Lateral Inherently Thin (LIT) amorphous-crystalline silicon heterojunction PV device. Benchmarked theoretical studies of the devices, using Sentaurus - a device modelling code, indicate a maximum BACH cell and LIT cell efficiency of 24.4% and 23.9%, respectively, for a 100µm thick textured cSi substrate with attainable (10 cm/sec) passivation quality. BACH and LIT PV devices, integrating the new facile grown SiOx passivation scheme, were fabricated using n-type double-side polished 280µm thick (100) FZ cSi wafers. An optimal untextured cell efficiency of 16.7% and 11.6% are obtained for a 1 cm2 BACH and LIT devices, respectively, under AM1.5 solar irradiation. Development of the high quality facile grown oxide based passivation scheme, a paradigm shift relative to conventional thermal oxide passivation, paves the path for low-temperature synthesis of oxide-based high quality semiconductor devices on thin silicon - including high-efficiency silicon photovoltaics.
Deciphering X-chromosome inactivation and the role of MECP2e1 in Rett Syndrome patient induced pluripotent stem cells
Keywords: Rett Syndrome
Induced Pluripotence

Rett Syndrome (RTT) is a neurodevelopmental disorder that affects girls due primarily to heterozygous mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). MECP2 encodes four exons that are alternatively spliced into two isoforms, MECP2e1 and MECP2e2. MECP2 isoform-specific functions are unknown, but due to the higher abundance in the brain and MECP2e1-specific mutations associated with RTT, MECP2e1 is hypothesized to be the functional isoform in the brain. MECP2 is an X-linked gene subject to random X-chromosome inactivation (XCI) resulting in mosaic expression of mutant MECP2. The lack of readily accessible human brain tissue motivates the need for alternative human cellular models to study RTT. In this thesis, I established a novel human in vitro model of RTT by isolating human induced Pluripotent Stem cells (hiPSCs) from RTT patient fibroblasts. RTT-hiPSCs retained the MECP2 mutation, are pluripotent and fully reprogrammed, and retained an inactive X-chromosome in a nonrandom pattern. Taking advantage of the latter characteristic, I obtained a pair of isogenic wild-type and mutant MECP2 expressing RTT-hiPSC lines that retained this MECP2 expression pattern upon differentiation into neurons. Phenotypic analysis of mutant RTT-hiPSC-derived neurons demonstrated a reduction in soma size compared with the isogenic control RTT-hiPSC-derived neurons from the same RTT patient validating RTT-hiPSC-derived neurons for disease phenotyping. To further understand the role of MECP2e1 in RTT, I took advantage of RTT-hiPSCs carrying a MECP2 mutation that specifically disrupts MECP2e1 while MECP2e2 remains intact (RTTe1). RTTe1-hiPSC-derived neurons exhibited a soma size defect compared to wild-type neurons. Furthermore, this phenotype was rescued by MECP2e1 vectors in a cell autonomous manner suggesting that disruption of MECP2e1 alone is sufficient to cause a cellular RTT phenotype. Altogether, in this thesis, I isolated mutant and isogenic control RTT-hiPSCs by taking advantage of their unique XCI pattern. Upon differentiation, mutant RTT-hiPSC-derived neurons exhibited a RTT phenotype compared to isogenic control hiPSC-derived neurons from the same patient. Analysis of mutant and isogenic control hiPSC-derived neurons represents a novel human in vitro model for understanding the pathogenesis of RTT and the role of MECP2 and its isoforms in human neurons.
The Dark and Bright Sides of Anxiety: A Comprehensive Examination of the Relation between State Anxiety, Trait Anxiety, and Job Performance
Keywords: Anxiety
Job Performance
Motivation

Research has consistently tapped into a “dark side” of anxiety by demonstrating that anxiety has a negative relation with performance, while neglecting to consider the possibility of a “bright side” of anxiety by examining whether anxiety can benefit performance. The purpose of this research was to conduct a comprehensive examination of the anxiety and job performance relationship by considering the potential for a dark and bright side. First, I developed a dual-process model of anxiety outlining the process through which state and trait anxiety might lead to debilitative and facilitative job performance. Drawing from Interference Theory (Wine, 1980), I predicted that anxiety leads to debilitative performance through off-task cognition. Drawing from the Integrative Resource Model (Kanfer & Ackerman, 1989), Processing Efficiency Theory (Eysenck & Calvo, 1992), and Attentional Control Theory (Eysenck, Derakshan, Santos, & Calvo, 2007), I predicted that anxiety leads to facilitative performance through self-regulatory processing. Second, guided by motivation theory (Vroom, 1964), I extended my theoretical model by specifying a condition under which anxiety might lead to debilitative and facilitative performance. Specifically, motivation is predicted to moderate the relationship between anxiety and off-task cognition, and between anxiety and self-regulatory processing. Two controlled laboratory experiments tested the overall model. Experiment 1 consisted of a simulated work environment with 306 participants. Experiment 2 consisted of a similar work simulation with 327 participants. In both experiments, trait anxiety was assessed through self-report, three levels of state anxiety were induced in participants, and performance on in-basket tasks was examined. Experiment 2 also manipulated two levels of motivation. Findings do not support a bright side of anxiety and suggest that the dark side of anxiety is quite robust. Both trait and state anxiety led to higher levels of off-task cognition, which led to lower performance. Both trait and state anxiety led to lower levels of self-regulatory processing, which led to higher performance. Experiment 2 extended these results by finding that motivation buffered the relationship between state anxiety and self-regulatory processing, and between state anxiety and off-task cognition. Motivation did not have an effect for trait anxiety. Contributions and practical implications are discussed.
Three Essays on the Impact of Geographic and Social Proximity on Innovation
Keywords: microgeography
idea recombination
low-opportunity cost time
colocation
proximity

The ability of an economy to generate and diffuse ideas has a profound influence on its ability to sustain growth. Our understanding of a key economic phenomenon behind agglomeration and modern growth - localization economies - relies on basic assumptions about how knowledge is recombined locally versus over distance. Whereas scholars have extensively studied the effects of proximity on the diffusion of ideas, the micro-foundations of knowledge recombination remain undeveloped. In particular, we know surprisingly little about how geographic, social and knowledge proximity shape the way ideas are generated, recombined, and discovered by others. In the first study, I provide novel empirical evidence grounded in an original theoretical framework to explain how the composition of near-neighbor scientists influences the direction of inventive activity. Co-located individuals are more likely to engage in low expected value but high variance payoffs interactions ("water cooler"). To address endogeneity concerns due to selection into co-location and matching, I exploit an unexpected random relocation of scientists due to asbestos removal at UPMC Paris. Results are consistent with the theory and shed light on how proximity affects innovation: random versus chosen co-location leads to higher levels of experimentation, and has a positive impact on breakthrough ideas for collaborations across academic fields. In the second study I explore the decline in collaboration that follows the separation of previously co-located co-authors. Not all co-author pairs are equally affected by an increase in geographic distance, as social proximity substitutes for it when the returns to collaboration are high. Collaborations that bridge otherwise disconnected communities of experts are the most negatively affected by separation. Finally, the third study examines how social and geographic proximity affect the discovery and funding of creative projects in online crowdfunding. Whereas the internet reduces many distance-related frictions, local and distant investors exhibit different investment patterns. The distance effect is explained by investors who likely have a social relationship with the entrepreneur, and does not persist after the first investment (i.e., it is likely driven by search costs). Thus, crowdfunding seems to eliminate many distance-related frictions, but not those related to social interactions.
Ambivalent Visions: Dreams, Bereavement, and Belonging in Contemporary Canadian Memoirs
Keywords: Memoir
Dreams
Visions
Bereavement
Mourning
Displacement

This study examines the prominent intersections between dreams, representations of bereavement, and negotiations of social and geographic belonging in ten contemporary Canadian memoirs. Dreams are a remarkably common device in the genre, most often appearing in accounts of family members' deaths or staging encounters with deceased others and originary landscapes. I argue that these dreams operate as ambiguously authorizing and paradoxically reassuring spaces of contradiction and reconnection that convey the ambivalence of contemporary responses to death and displacement. As such, I suggest that dreams are prevalent in memoirs because they align with the genre's characteristic focus on personal and social relationships and its irresolvable tensions between representations of self and other, private and public, and desire and detachment. The four chapters theorize dreams through the lenses of bereavement studies, elegy studies, diaspora studies, and body and affect studies, considering how they adapt the conventions of literary modes such as dream-vision, elegy, and pastoral to address contemporary concerns. Chapter One argues that memoirs frequently link premonitory dreams, deathbed visions, and dreams of the dead in 'narratives of dying' that assert the possibility of continued subjectivity after death, with reference to memoirs by Daphne Marlatt, Wayson Choy, and Philip Roth. Chapter Two considers the similarities between the use of dreams in memoirs and poetic elegies, analyzing memoirs and poetry by Lorna Goodison and Patrick Lane to argue that dreams problematize the possibility of speaking for the dead and act as a form of elegiac compensation in both genres. Chapter Three examines diasporic memoirs by Wayne Johnston, Janice Kulyk Keefer, and Michael Ondaatje, theorizing the circumscribed, originary landscapes depicted in dreams as sites of simultaneous nostalgia and irony, reminiscent of complex forms of the pastoral. Finally, Chapter Four argues that memoirs' tendency to privilege embodied and affective responses to dream experience enables memoirists such as Choy, Rudy Wiebe, and Sharon Butala to claim affective affiliations that extend beyond the family. Ultimately, this study posits that dreams’ ability to articulate relational tensions within a solipsistic psychological form offers a strategically non-committal and open-ended way of representing loss and belonging in contemporary Canadian memoirs.
Inferring Body Mass in Extinct Terrestrial Vertebrates and the Evolution of Body Size in a Model-Clade of Dinosaurs (Ornithopoda)
Keywords: Evolution
Body Size
Body Mass Estimation
Limb Scaling
Volumetric Reconstructions
Dinosauria
Tetrapoda
Quadrupedal
Bipedal
Macroevolution
Adaptive Radiation
Cope's Rule
Island Rule
Ornithopoda
Hadrosauridae
Theropoda
Regression
Evolutionary Models
Mammalia
Reptilia
Aves

Organismal body size correlates with almost all aspects of ecology and physiology. As a result, the ability to infer body size in the fossil record offers an opportunity to interpret extinct species within a biological, rather than simply a systematic, context. Various methods have been proposed by which to estimate body mass (the standard measure of body size) that center on two main approaches: volumetric reconstructions and extant scaling. The latter are particularly contentious when applied to extinct terrestrial vertebrates, particularly stem-based taxa for which living relatives are difficult to constrain, such as non-avian dinosaurs and non-therapsid synapsids, resulting in the use of volumetric models that are highly influenced by researcher bias. However, criticisms of scaling models have not been tested within a comprehensive extant dataset. Based on limb measurements of 200 mammals and 47 reptiles, linear models were generated between limb measurements (length and circumference) and body mass to test the hypotheses that phylogenetic history, limb posture, and gait drive the relationship between stylopodial circumference and body mass as critics suggest. Results reject these and instead recover a highly conserved relationship that provides a robust method to estimate body mass in extinct quadrupedal tetrapods. The constrained model is then used to derive a mathematical correction that permits the body mass of bipedal taxa to be estimated from the quadrupedal-based equation. These equations thus form the empirical baseline dataset with which to assess the accuracy of mass estimates derived from volumetric reconstructions, which, although subjective, are crucial for interpreting biomechanical and physiological attributes in extinct forms. The models developed through this research provide accurate and consistent estimates of body size in terrestrial vertebrates, with important implications for generating large datasets aimed at reconstructing macroevolutionary patterns of body size in association with changing Earth systems.