VictorJuiz/thesis huggingface dataset:
Metamemory Processes in Persons with Schizophrenia
Keywords: schizophrenia
metamemory
memory
metacognition

Memory impairment in Schizophrenia (SCZ) is robust and associated with poor functional outcome. However, these correlations are only moderate in magnitude, leading some researchers to propose that metamemory deficits may also underpin poor memory performance and related functional deficits in this population. The purpose of this dissertation was to assess various aspects of metamemory performance among persons with SCZ. The studies are organized along a temporal continuum of metamemory processes, operating from retrieval to output. Study 1 evaluated whether persons with SCZ control retrieval by re-instating the processing mode employed at encoding (i.e., source-constrained retrieval). Participants studied words under deep or shallow conditions and then completed two recognition tests – a standard test followed by the memory-for-foils test (i.e., foils from the first test become targets on the second test). Only HCs in the deep encoding condition exhibited superior memory for foils, suggesting diminished source-constrained retrieval among persons with SCZ. In study 2, criterion setting and adjusting was investigated by altering the relative distinctiveness between lures and targets on two separate recognition tests. Persons with SCZ set a stricter criterion but adjusted it appropriately in response to lure distinctiveness (i.e., difficulty). In study 3, the strategic regulation of response granularity (i.e., from fine [e.g., 1:20 pm] to coarse [e.g. afternoon] was investigated by manipulating monetary incentives and penalties. Results show that persons with SCZ are overconfident in their memories and impaired in modulating granularity. Collectively these studies suggest a pattern of both intact and deficient metamemory skills characterize persons with SCZ. Possible underlying mechanisms and functional implications of this pattern are discussed.
Visualizing Invisibles with Single-molecule Techniques: from Protein Folding to Clinical Applications
Keywords: single molecule spectroscopy
dark state
protein folding
capillary electrophoresis

Single-molecule fluorescence spectroscopy techniques such as Fluorescence Correlation Spectroscopy (FCS) and single-molecule Förster Resonance Energy Transfer (smFRET) not only possess an unprecedented high sensitivity but also have high temporal and spatial resolution. Therefore, they have an immense potential both in investigation of fundamental biological principles and in clinical applications. FCS analyses are based on both theoretical approximations of the beam geometry and assumptions of the underlying molecular processes. To address the accuracy of analysis, firstly the experimental conditions that should be fulfilled in order to obtain reliable physical parameters are discussed and the input parameters are carefully controlled accordingly to demonstrate the performance of FCS measurements on our home-built confocal multiparameter photon-counting microscope in several in vitro and in-vivo applications. Secondly, we performed a comprehensive FCS analysis of rhodamine family of dyes to evaluate the validity of assigning the correlation relaxation times to the time constant of conformational dynamics of biomolecules. While it is the common approach in literature our data suggests that conformational dynamics mainly appear in the correlation curve via modulation of the dark states of the fluorophores. The size and shape of the folded, unfolded and chemically-denatured states of the N-terminal Src-homology-3 of downstream of receptor kinases (DrkN SH3) were investigated by FCS and smFRET burst experiments. Based on the data, we conclude that a considerable sub-population of the denatured protein is in a closed loop state which is most likely formed by cooperative hydrogen bonds, salt bridges and nonpolar contacts. As a clinical application, we developed and characterized an ultrasensitive capillary electrophoresis method on our multiparameter confocal microscope. This allowed us to perform Direct Quantitative Analysis of Multiple microRNAs (DQAMmiR) with about 500 times better sensivity than a commercial instrument. Quite remarkably, we were able to analyze samples of cell lysate down to the contents of a single cell.
Identification of Converging Pathways in the pathogenesis of NPM-RARA Variant Acute Promyelocytic Leukemia
Keywords: Leukemia
Nucleophosmin

Acute Promyelocytic Leukemia is a subset of Acute Myeloid Leukemias, and is commonly associated with the presence of chromosomal translocations leading to the expression of the PML-RARA fusion protein. Less frequent cases of APL have been identified that express rare variant RARA fusion proteins, such as NPM-RARA. The presence of these fusions results in deregulated RARA signaling and response to the RARA ligand, ATRA. However, studies have indicated that loss of retinoid signaling alone is not sufficient to result in the leukemia. The goals of this thesis were to determine genes and pathways deregulated in variant APL that can serve as cooperating events in APL, through candidate pathway analysis and high-throughput gene expression profiling. Using a cell line model expressing variant fusion proteins associated with APL, we identified the deregulation of the NF-kappaB signaling pathway in APL, and describe the functional analysis of this pathway in our in vitro model. We next assessed whether promotion of survival signals could serve as a contributing factor in the accumulation of leukemic blasts in APL patient bone marrow. Our results indicated that PML-RARA and NPM-RARA expressing cells showed increased survival in the presence of TNFalpha, compared to wild type control cells. These data suggested a greater ability on the part of NPM-RARA cells to survive in the presence of TNFalpha. We also report for the first time the gene expression profiles of, and transcriptional effects of ATRA on, cells expressing the variant fusion proteins. Finally, we determined that the partner protein Nucleophosmin (NPM) has increased cytoplasmic localization in cells expressing the APL fusion proteins, and interacts within complexes comprising of RARA and RXRA. We further determined that the fusion can interfere with NPM function and cellular localization. Taken together, these studies provide evidence for the involvement of secondary hits in APL biology.
Self-determination in Health Care: A Multiple Case Study of Four First Nations Communities in Canada
Keywords: First Nations
public health
Aboriginal
health care policy
Canada
self government
self determination

The perceived level of self-determination in health care in four First Nations communities in Canada is examined through a multiple case study approach. Twenty-three participants from federal, provincial and First Nations governments as well as health care professionals in the communities of Blood Tribe, Lac La Ronge, Garden Hill and Wasagamack First Nations provided insight into the diversity of perception of self-determination in First Nations health care. The difference in definition between Aboriginal and the federal and provincial governments is a factor in the varying perceptions of the level of control First Nations communities have over their health care system. Participants from the four First Nations communities perceived their level of self-determination over their health care system to be much lower than the level perceived by provincial and federal government participants. The organization and delivery of health care is based on the location of the community, the availability of the human resources, the level of communication, the amount of community resources, and the ability to self-manage. The socio-political history including impact of contact, residential schools, and integration of Aboriginal worldview are factors in the organization and delivery of health care as well as the perceived level of self-determination that the community sees. The duration and intensity of contact influences how health care is organized as the communities become more familiarized with the biomedical model that most Canadians use. Having a holistic health care system that includes acknowledging the socio-political history, culture, language, worldview and traditional medicines is important to the four First Nations communities, but this has not been fully embraced in any of the communities. Despite their differences, all four communities are working toward self-determination that hopefully would result in an ‘ideal’ First Nations health care system which is holistic, cultural, spiritual, and interdisciplinary and ultimately lead to full management of the health care system.
Chronic Effects and Acute Physiological Response to Aerobic and Resistance Training in Patients Following Stroke Referred to a Cardiac Rehabilitation Program
Keywords: Cerebrovascular Event
Exercise Therapy

There is compelling evidence that regular physical activity is likely to play a role in the secondary prevention of stroke and comorbid coronary artery disease. However, structured physical activity programs are not widely available for people following stroke. Cardiac rehabilitation programs (CRP) are well suited to provide exercise training following traditional stroke rehabilitation. However, people following stroke may be limited by a constellation of neurological deficits that may prevent them from effectively participating in and benefiting from an adapted CRP. Accordingly, the objectives of this work were to 1) examine the utility of cardiopulmonary exercise stress testing (CPET) for developing an exercise prescription in people ≥3 months post-stroke with mild/moderate motor impairments 2) determine ability to achieve minimal recommended exercise training levels reported to elicit health benefits during a single standard CR session following completion of a CRP 3) evaluate the physiological, and cognitive effects of a 24-week CRP of resistance and aerobic exercise and the effect of stroke-recovery-time. It was hypothesized that most patients (>50%) would reach a level of exertion on the CPET that would provide recommended exercise prescription target levels and that individuals would be able to systematically reach these target levels during a CR session. Moreover, the established exercise program would result in physiological and cognitive benefit independent of time-from-stroke. Study 1 demonstrated that most patients achieved a level of exertion during the CPET sufficient to inform an exercise prescription. In Study 2 patients with motor impairments were able to meet or exceed minimal recommended exercise target levels of intensity, duration and energy expenditure. In Study 3 a CRP yielded improvements over multiple domains of recovery (cardiovascular fitness, functional ambulation, sit-to-stand performance, and muscular strength). While those referred ≤1 year and >1 year post-stroke derived benefits from a CRP, those who started earlier (≤1 year) had greater improvements in ambulatory performance. In Study 4 combined aerobic and resistance exercise resulted in improvements in cognitive function. Change in cognition was positively associated with change in fat-free mass and change in anaerobic threshold. In summary people post-stroke are able to effectively participate in and benefit from an adapted CRP.
The Dentate Gyrus of the Hippocampus: Roles of Transforming Growth Factor beta1 (TGFbeta1) and Adult Neurogenesis in the Expression of Spatial Memory
Keywords: adult neurogenesis
transforming growth factor-beta
hippocampus
Dentate gyrus
cognition

The dentate gyrus is a region that hosts most of the hippocampal cells in mammals. Nevertheless, its role in spatial memory remains poorly understood, especially in light of the recently-studied phenomenon of adult hippocampal neurogenesis and its possible role in aging and chronic brain disease. We found that chronic over-expression of transforming growth factor beta1 (TGFbeta1), a cytokine involved in neurodegenerative disease, results in several modifications of brain structure, including volumetric changes and persistent astrogliosis. Furthermore, TGFbeta1 over-expression affects the generation of new neurons, leading to an increased number of neurons in the dentate gyrus and deficits in spatial memory acquisition and storage in aged mice. Nonetheless, reducing neurogenesis via pharmacological treatment impairs spatial memory in juvenile mice but not in adult or aged mice. This suggests that the addition of new cells to hippocampal circuitry, and not the increased plasticity of these cells, is the most relevant role of neurogenesis in spatial memory. We tested this idea by modifying proliferation in the dentate gyrus at several ages using multiple techniques and evaluating the incorporation of newborn neurons into hippocampal circuitry. We found that all granule neurons, recently generated or not, have the same probability of being incorporated. Therefore, the number of new neurons participating in memory circuits is proportional to their availability. Our conclusion is that adult-generated cells have the same functional relevance as those generated during development. Together, our data show that the dentate gyrus is important for memory processing and that adult neurogenesis may be relevant to its functionality by optimizing the number of neurons for memory processing. The equilibrium between neurogenesis and optimal dentate gyrus size is disrupted when TGFbeta1 is chronically increased, which occurs in neurodegenerative pathologies, leading to cognitive impairment in aged animals.
A Framework for the Development of Scalable Heterogeneous Robot Teams with Dynamically Distributed Processing
Keywords: robot teams
control system architecture
distributed
heterogeneous
failure recovery
SLAM
hardware-in-the-loop

As the applications of mobile robotics evolve it has become increasingly less practical for researchers to design custom hardware and control systems for each problem. This research presents a new approach to control system design that looks beyond end-of-lifecycle performance and considers control system structure, flexibility, and extensibility. Toward these ends the Control ad libitum philosophy is proposed, stating that to make significant progress in the real-world application of mobile robot teams the control system must be structured such that teams can be formed in real-time from diverse components. The Control ad libitum philosophy was applied to the design of the HAA (Host, Avatar, Agent) architecture: a modular hierarchical framework built with provably correct distributed algorithms. A control system for exploration and mapping, search and deploy, and foraging was developed to evaluate the architecture in three sets of hardware-in-the-loop experiments. First, the basic functionality of the HAA architecture was studied, specifically the ability to: a) dynamically form the control system, b) dynamically form the robot team, c) dynamically form the processing network, and d) handle heterogeneous teams. Secondly, the real-time performance of the distributed algorithms was tested, and proved effective for the moderate sized systems tested. Furthermore, the distributed Just-in-time Cooperative Simultaneous Localization and Mapping (JC-SLAM) algorithm demonstrated accuracy equal to or better than traditional approaches in resource starved scenarios, while reducing exploration time significantly. The JC-SLAM strategies are also suitable for integration into many existing particle filter SLAM approaches, complementing their unique optimizations. Thirdly, the control system was subjected to concurrent software and hardware failures in a series of increasingly complex experiments. Even with unrealistically high rates of failure the control system was able to successfully complete its tasks. The HAA implementation designed following the Control ad libitum philosophy proved to be capable of dynamic team formation and extremely robust against both hardware and software failure; and, due to the modularity of the system there is significant potential for reuse of assets and future extensibility. One future goal is to make the source code publically available and establish a forum for the development and exchange of new agents.
To Cue or Not to Cue: Beacons and Landmarks in Object-displacement Tasks
Keywords: object-displacement task
landmark
beacon
cue use
toddler search

Two experiments examined the role of various cues on children’s performance in a well-known object-displacement task. In this task, children observed a toy rolling down a ramp whose trajectory was occluded by an opaque screen with doors. A barrier was placed along the ramp, behind one of the doors, to stop the toy. The top portion of the barrier was visible above the screen. To search successfully, children had to retrieve the hidden toy by opening the correct door. Previous work had found that the barrier was an ineffective cue among children less than three years of age. According to a landmark-based account, this was because the barrier was only an indirect cue to object location. If a cue directly marked the location, then it would be more likely attended and utilized. This model underscores the spatial relation between cue and the target. Other cue properties are important in so far that they modify this spatial relation. In Experiment 1, a cue’s distance from the target object was manipulated (i.e., short vs. long), but the location marked by the cue was kept constant (i.e., correct door was directly below). The search performances of 24- and 30-month old children were compared under no cue, short-cue/short-door, and long-cue/long-door conditions. Both age groups performed equally well under both cued conditions. In Experiment 2, a cue’s movement (i.e., coincident with the car vs. not coincident with the car) down the ramp was manipulated. The performance of 24- and 30-month old children were compared under attached-direct cue and unattached-direct cue conditions. Both age groups performed well under both conditions. Collectively, the results provide support for the landmark-based account. The spatial relation between cue and target underlies toddlers’ search. Properties of the cue matter to the extent that they impact how well the cue marks its target.
New Insights into the Evolutionary Mantenance of Male Mate Choice Behaviour using the Western Black Widow Spider, Latrodectus hesperus
Keywords: male mate choice
genital mutilation
mating plugs
spiders
natural populations
sexual selection

Mate choice among males is relatively understudied, despite recent evidence supporting its ubiquity. Theory predicts male mate choice in response to variation in female quality, and male mating strategies that limit polygyny. However empirical research investigating these connections, particularly under natural conditions, is generally lacking. Using the Western black widow spider, Latrodectus hesperus, I investigated male mate choice, male investment, and the advantage of mating with females that differ in their potential to deliver fitness benefits to males via higher fecundity and/or reduced risk of sperm competition. Males were found to be preferentially attracted to larger, high-diet virgin females over females that were smaller due to a lower diet, or having been previously mated, or both. Through a three-year field study on females I found that males likely benefit from selectivity, as smaller, low-diet females often failed to deposit any egg sacs throughout the breeding season, likely due to their shortened web-site tenure and/or lack of bodily resources. I investigated the costs and benefits to male genital breakage in L. hesperus, a strategy typically assumed to result in male sterility while providing paternity protection. I found that genital mutilation in L. hesperus did not cause sterility and that males were capable of inseminating multiple females, likely because of the comparatively low amount of genital damage and the likelihood of the efficient placement of genital fragments. Evidence from double mating trials supported the efficacy of broken genital fragments as plugs, but first male sperm precedence was often maintained in cases where male genital breakage failed or fragments were positioned incorrectly, which occurred frequently. Together, these laboratory and field experiments contribute to a more complete view of mate choice.
Interpreting Variability through Multiple Methodologies: The Interplay of Form and Function in Epipalaeolithic Microliths
Keywords: lithic analysis
Epipalaeolithic

The reason and significance of variation in material culture is one of the most fundamental debates in archaeological studies. These debates factor strongly into Levantine Epipalaeolithic research, where the morphological variability of microlithic tools has been interpreted to represent distinct cultural or ethnic communities. This dissertation addresses microlith variability during the Middle Epipalaeolithic (≈17,500 – 14,600 cal BP) through the analysis of lithic assemblages from Wadi Mataha, ‘Uyun al-Hammâm, and Kharaneh IV (Jordan). Although regionally disparate, the lithic assemblages are characterized by the same geometric microlith type: the trapeze-rectangle. The integration of typological, technological, morphometric, and use-wear analyses allows for the subtleties in material culture to be explored among these sites. In addition to these analyses, new methods for use-wear quantification are presented. This dissertation sets out to test several hypotheses in regards to the microlith assemblages: 1) microliths will have overlapping functions, indicating that function does not drive form; and 2) microliths will show differences in technological style. These hypotheses relate back to current debates in Epipalaeolithic research about the nature of microlith variability. Is variation in microlith morphology the product of different technological sequences of production or microlith function? Or is variability the result of different cultural practices? This material culture variability is explored through the lens of the chaîne opératoire, where I advocate for the inclusion of functional analysis into our study of lithic assemblages. Through the integration of multiple methods, I suggest there is not a direct correlation between microlith form and function. Instead, the variability we witness in microliths during the Middle Epipalaeolithic is the result of local expressions within different communities.