VictorJuiz/thesis huggingface dataset:
The Identification and Characterization of Evolutionarily Conserved Transcription Factors Required for Brain Regeneration in Flatworms
Keywords: Brain Regeneration
GABA
neural progenitor
Planaria
TCF/LEF
WNT signaling

Powerful genetic tools in classical laboratory models have been fundamental to our understanding of how stem cells give rise to complex neural tissues during embryonic development. In contrast, adult neurogenesis in our model systems, if present, is typically constrained to one or a few zones of the adult brain to produce a limited subset of neurons leading to the dogma that the brain is primarily fixed post-development. The freshwater planarian (flatworm) is an invertebrate model system that challenges this dogma through its continuous neuronal cell turnover and the ability to rapidly regenerate a brain de novo after injury. My aims in this thesis were to identify and characterize regulators of flatworm regenerative adult neurogenesis to gain a deeper understanding of the fundamentals of unlimited adult regenerative neurogenesis. I found that members of the basic helix-loop-helix gene family are required to regenerate a brain. Additionally, I identified a planarian TCF/LEF transcription factor Smed-tcf1 as required for the proper regeneration of several dorsal-lateral neural populations including GABAergic neurons.
Audiovisual Processing and Integration in Amblyopia
Keywords: Amblyopia
Audiovisual integration
Audiovisual processing
Multisensory integration
Multisensory processing
Psychophysics

Amblyopia is a developmental visual disorder caused by abnormal visual experience during early life. Accumulating evidence points to perceptual deficits in amblyopia beyond vision, in the realm of audiovisual multisensory perception. This thesis presents a systematic psychophysical investigation of audiovisual processing and integration in adults with unilateral amblyopia. Study I examines audiovisual spatial integration and reveals amblyopic deficits in localization precision for unisensory visual and auditory stimuli, but statistically optimal integration according to the maximum likelihood estimation model of multisensory integration. Study II confirms the novel deficit in sound localization described in Study I, and reveals a non-uniform spatial pattern of sound localization deficits that implicates the superior colliculus as a primary neural locus affected by abnormal visual experience. Study III measures audiovisual simultaneity perception, and shows that asynchronous audiovisual pairs are perceived as synchronous over wider temporal intervals than normal, regardless of which eye is viewing. Study IV examines audiovisual temporal integration using the temporal ventriloquism effect, and reveals successful temporal integration in amblyopia, but possibly over a wider interval of audiovisual asynchrony. In sum, the findings suggest that the capacities for spatial and temporal audiovisual integration are intact in amblyopia, but that non-integrative multisensory processes, including cross-modal temporal matching and cross-sensory calibration of sound localization, are impaired.
Elucidation of the Mechanisms of Transcellular and Paracellular Endothelial Permeability -- Towards its Therapeutic Manipulation
Keywords: Atherosclerosis
Endothelium
Inflammation
Influenza
LDL
Permeability

Every blood vessel in the body is lined on its luminal aspect with a single layer of interconnected cells, known as endothelial cells. Together, these cells form a tissue known as the endothelium, a tightly regulated system that physically segregates the fluid in the blood from the peripheral tissues, and orchestrates the passage of nutrients, xenobiotics, immune cells, and fluids between distinct compartments in the body. In healthy, quiescent vasculature, passage of compounds across the vasculature occurs by two separate, yet equally important mechanisms. In the paracellular route, compounds that are small enough to pass between endothelial cell junctions freely diffuse down their concentration gradient, reaching equilibrium between the blood and sub-endothelial compartments. In contrast, transcytosis involves the regulated transit of compounds through endothelial cells by endocytosis, subcellular trafficking, and exocytosis, and in doing so, allows for the transport of larger compounds through the use of a number of specialized proteins. Under normal circumstances, these two mechanisms of endothelial permeability work in concert to maintain homeostasis. However it has recently become apparent that dysregulated endothelial permeability is the cause of a number of pathological conditions. Increased paracellular permeability of the lung endothelium leads to the acute respiratory distress syndrome (ARDS), a potentially fatal condition involving acute lung edema, respiratory failure, and death. Endothelial transcytosis of low-density lipoprotein (LDL) leads to the accumulation of LDL in the subendothelial intima, the initiating event in atherosclerotic lesion development. Although dysregulated endothelial permeability is central to the pathophysiology of these diseases, the paucity of literature on the subject highlights the need for a detailed, mechanistic investigation. In this thesis I present a body of work that uncovers several novel mechanisms that regulate endothelial permeability in the pathological contexts of pathogen-induced ARDS and LDL transcytosis as a precursor to atherosclerotic lesion development. Results from these studies suggest that targeting endothelial permeability is novel and viable therapeutic strategy for management of these common diseases.
Natural and Anthropogenic Influences on High Arctic Aerosol
Keywords: aerosol
aerosol mass spectrometry
Arctic
long range transport
organic aerosol

The Arctic is a harbinger of global change, and is warming at a rate twice the global average. While Arctic warming is driven by increased greenhouse gases, short-lived climate forcers such as tropospheric ozone and aerosol are important drivers of Arctic climate. Aerosol impacts on Arctic climate are insufficiently understood, largely owing to poor constraints on the physical and chemical processes controlling aerosol. This thesis presents observations of sub-micron aerosol in Arctic summer and spring, which capture different regimes of the Arctic aerosol seasonal cycle. Aircraft-based observations of aerosol physical and chemical properties address various aspects of Arctic aerosol sources, removal and chemical processing. Under chronic Arctic Haze conditions in spring, we observed evidence for vertical variations in both aerosol sources and removal mechanisms. We show evidence for sources of partially neutralized aerosol with higher organic aerosol (OA) and black carbon content in the mid-troposphere and sources of acidic sulfate in the lower troposphere. With support from model calculations, we demonstrate that mid-tropospheric air influences the Arctic Boundary Layer (ABL) on ~1-week time scales. We observed evidence for aerosol depletion relative to carbon monoxide, both in the mid-to-upper troposphere and within the ABL. Dry deposition, with low removal efficiency, contributed to aerosol removal in the ABL while precipitation scavenging contributed to efficient aerosol removal during transport at higher altitudes. Under clean Arctic background conditions in summer, we observed evidence for marine influenced secondary OA formation. We demonstrated a relationship between methansulfonic acid and OA with the residence time of air over open water. Sea salt aerosol was externally mixed from a larger number fraction of OA, sulfate and amine-containing particles. High OA fractions coincided with elevated cloud condensation nuclei (CCN) concentrations, suggesting a role for secondary OA formation in growing particles to CCN-active sizes. A case study of aerosol growth over open water supports these observations. This work contributes to our understanding of aerosol vertical variability and its connection to observations made at the surface in Arctic spring and, to our understanding of aerosol sources and composition in Arctic summer.
Detecting Protein Variants within Mass Spectrometry Datasets
Keywords: Integrative -omics
mass spectrometry
Proteogenomics
Proteomics
Variant protein detection

An important aim of cancer proteomics is to understand how the cancer proteome, with all its variation in both protein sequence and protein abundance, emerges from aberrations characterized within cancer genomic and transcriptomic datasets. A challenge in reaching this goal is that standard mass-spectrometry-based onco-proteomic strategies typically ignore variations in protein sequences, instead characterizing cancer proteomes in terms of changing abundances of standard reference proteins. In this thesis, I assess strategies for incorporating information about protein sequence variation within standard proteomics analysis strategies. I develop a pipeline for the characterization of variations within protein sequences and assess the best methodology to do so.
Collective motion of chemically powered nanomotors
Keywords: Collective motion
GPU
Molecular dynamics
Multiparticle collision dynamics
Nanomotor
Self-propelled particles

Self-propelled chemically powered synthetic micron- and nano-scale motors are being intensively studied because of the wide range of potential applications that exploit their directed motion. The collective behavior of chemically powered sphere-dimer motors made from linked catalytic and noncatalytic spheres in a quasi-two-dimensional confined geometry is studied using a coarse-grain microscopic dynamical model. Chemical reactions at the catalytic spheres that convert fuel to product generate forces that couple to solvent degrees of freedom as a consequence of momentum conservation in the microscopic dynamics. The collective behavior of the many-body system is influenced by direct intermolecular interactions among the motors, chemotactic effects due to chemical gradients, hydrodynamic coupling, and thermal noise. Segregation into high and low density phases and globally homogeneous states with strong fluctuations are investigated as functions of the motor characteristics. Factors contributing to this behavior are discussed in the context of active Brownian models. Like their larger micron-scale counterparts, Angstrom-scale chemically powered motors use asymmetric catalytic activity to produce self-generated concentration gradients that lead to directed motion. Unlike their micron-scale counterparts, Angstrom-scale motors are dominated by fluctuations, molecular reorientation often occurs on picosecond time scales limiting the regime where ballistic motion dominates, and solvent sizes are often comparable to those of the motor, so structural effects come into play and solvent depletion forces are very strong. These new features are studied using full molecular dynamics simulations of an Angstrom-scale sphere-dimer motor. The properties of an Angstrom-scale sphere-dimer motor confined between two planar walls separated by distances of tens of nanometers are investigated. The simulations were carried out on many tightly-coupled graphics processing units (GPU) using two massively parallel codes, Nano-dimer and Angstrom-dimer that have been published under a free-software license.
Insane in the Membrane: The Functional Assembly of a G Protein Coupled Receptor at the Single-Molecule Level
Keywords: fluorescence microscopy
fluorescence spectroscopy
GPCR
G protein
oligomerization

Many aspects of cellular signaling pathways regulated by G protein coupled receptors (GPCRs) are not completely understood. In particular, two questions have been the focus of much attention and debate: the oligomeric status of the receptor-G protein signaling complex, and the coupling state between the receptor and the G protein in response to external stimuli. Using single molecule fluorescence spectroscopy and microscopy, we investigated these two questions with a focus on the M2 muscarinic acetylcholine receptor and the attendant Gi protein. The oligomeric status of the M2 receptor and of the Gi protein was first determined using dual-color fluorescence correlation spectroscopy (dcFCS). Positive cross-correlation between differently labeled M2 receptors and differently labeled Gi proteins was observed for samples either purified in detergent solution or expressed in live cells, indicating the existence of oligomeric M2 receptors and oligomeric Gi proteins. The oligomeric sizes of both proteins were then quantitatively measured by single molecule photobleaching (smPB) on a total internal reflection fluorescence (TIRF) microscope. Upon surface immobilization, M2 receptors were found to exist primarily as tetrameric complexes, whereas Gi proteins were found to exist as hexamers in the basal (inactive) state, and were reduced in size upon binding of GTP. Further evidence of oligomeric M2 receptors was found using smPB in fixed cells, in conjunction with an assessment of the fluorescence brightness analysis of single particles tracked in live cells. The coupling state between the M2 receptor and the Gi protein was first investigated using dcFCS. In the basal state without the receptor agonist, the amplitude of the cross-correlation was statistically close to zero between co-expressed and differently labeled M2 receptors and Gi proteins. This trend was the same for samples either purified in detergent or expressed in live cells. After receptor agonist was added, the amplitude of the cross-correlation curve increased significantly, indicating that the coupling between the M2 receptor and the Gi protein is transient and only induced by the agonist. The same agonist-induced MÂŹ2-Gi coupling interaction was also observed in our single particle tracking (SPT) studies of fluorescently labeled M2 receptors and Gi proteins in live cells.
Decomposing Trait and State Aspects of Regulatory Focus in Daily Life
Keywords: Emotion
Motivation
Personality
Psychology
Regulatory Focus

Regulatory focus theory describes two independent motivational systems, promotion and prevention focus, that regulate behavioural strategies toward desired goals (Higgins, 1997). Promotion focus prioritizes nurturance needs and achieving goals related to oneâ s hopes, dreams, and aspirations. Promotion focus also sensitizes a person to the presence and absence of rewards where success and failure are experienced as happiness and sadness, respectively. This is contrasted with prevention focus, which prioritizes safety needs and fulfilling oneâ s duties, responsibilities, and obligations. Prevention focus sensitizes a person to the presence and absence of losses where success and failure are experienced as calm and anxiety, respectively. The present study assessed emotion in daily life related to trait regulatory focus and success and their daily fluctuations in an experience sampling experiment. Participants completed a daily experiences survey every day for a month that measured their emotions and regulatory focus and success. The Big Five Personality dimensions were also measured to examine associations with individual differences in emotion. Regulatory focus predictions were only partially supported. In fact, regulatory focus was a consistently stronger predictor of daily emotion than success. Importantly, promotion focus was consistently related to more positive emotions and less negative emotions. In contrast, prevention focus was consistently related to more negative emotions and less positive emotions. Promotion focus also buffered against the negative emotions associated with goal failure as well as boosted the positive emotions associated with success. Conversely, prevention focus exacerbated the negative emotions of goal failure and attenuated the positive emotions associated with success. Personality also moderated different aspects of regulatory variables to predict different emotions. Decomposing regulatory focus and success into traits and daily fluctuations from trait levels predicted different emotions. Thus, to fully understand how regulatory focus influences emotion, success and focus must be differentiated at both the trait and day level.
Age-related changes in multisensory self-motion perception
Keywords: Aging
Integration
Motion
Multisensory
Optimal
Perception

To derive the precise estimates of self-motion necessary to perform mobility-related tasks like walking and driving, humans integrate information about their movement from across their sensory systems (e.g. visual, auditory, proprioceptive, vestibular). However, recent evidence suggests that the way in which multiple sensory inputs are integrated by the adult brain changes with age. The objective of this thesis was to consider, for the first time, whether age-related changes in multisensory integration are observed in the context of self-motion perception. Two research approaches were used. First, I used a simple, simulated driving task to provide visual cues to self-motion and to manipulate the availability of auditory and/or vestibular cues to self-motion (i.e., unisensory versus multisensory conditions). The results revealed that relative to younger adults, older adults generally demonstrate greater differences in performance between multisensory and unisensory conditions. However, the driving task could not disentangle the effects of age-related differences in real-world driving experience from age-related differences in sensory integrative mechanisms. Second, I used an established and highly controlled psychophysical heading perception task to evaluate whether, like younger adults, older adults integrate visual and vestibular cues to self-motion in a statistically optimal fashion. I considered conditions where each of the two cues was presented alone, in combination and congruent, or in combination but indicating conflicting heading angles. Results showed that while older adults did demonstrate optimal integration during congruent conditions, they were comparatively less tolerant to spatial conflicts between the visual and vestibular inputs. Overall, these results may have important implications for the way that older adults perform mobility-related tasks under various perceptual and environmental conditions.
Stories Women Weave: Merging community-based and academic interpretive approaches to style in wood splint baskets in the Upper New York State regional category of the Northeast basketry tradition.
Keywords: basket
Haudenosaunee
northeast
symmetry
women
wood splint

This dissertation explores patterned variability in Indigenous wood splint basket weaving within the Northeastern Woodlands Basketry Tradition. It focuses specifically on the groups that make up the Haudenosaunee confederacy in what is now classified as the Upper New York State regional category. This category has received considerably less attention than the other three regions in Northeastern North America. Basketry has been approached through both community-driven and academic methods, however, both focuse on different aspects of the industry. Academic discussions tend to focus on typologies, origins, and development, whereas community-driven discussions focus more on meaning and the importance of basketry to the communities. Academic researchers and basket making communities alike agree that baskets have the potential to transmit information and merging the information gathered by academic and community-driven research offers a more complete understanding of the Upper New York State basketry tradition. The purpose of this study is to explore the content of these messages present in wood splint baskets through time by using both academic and community-based research as complimentary to one another. The time period under investigation begins in the mid-19th century and continues to the present day. A total of 372 baskets from six museum collections were considered for this study. Block-stamped, hand-painted, and woven designs, common prior to A.D. 1860, were analyzed in terms the visual themes applied to the exterior of the basket. In addition, symmetry analysis was conducted on the themes woven directly into the basket forms on baskets made post A.D.1860. Results of the style analysis revealed decorative elements on both utilitarian and fancy baskets that refer to key cultural concepts that express and communicate themes such as seasonal ceremonies, and the importance of family, the land, and other beings on earlier utility style baskets. These themes do not disappear with the advent of fancy baskets. Rather, the designs woven directly into the fancy baskets are argued as metaphors for some of the same key cultural concepts found in the early baskets that govern the Haudenosaunee people. The designs become integrated in a more subtle way amidst the onslaught of assimilative pressures.
Gameplay In An Unfamiliar Environment: Novice and Expert Adult Players Encountering Portal For The First Time
Keywords: Game studies
Information practice
Information studies
Qualitative research
Video games

This thesis asks how adult video game players encounter an unfamiliar game for the first time by examining their gameplay. Gameplay is â the way a game is actually playedâ (Juul, 2005, p. 83). Players were invited to participate in a recorded gameplay session and share their reflections on their first encounter with Portal, a first-person puzzle video game. Using the video commentary model methodology with an exploratory approach, players reviewed and commented on their gameplay footage immediately following their session using a retroactive talk aloud protocol. These sessions were analyzed, comparing how different players encountered the game, how they identified challenges, and how they created solutions to those challenges. There was a noteworthy diversity in how different players encountered Portal with trends emerging amongst players with similar expertise. Novice players found it more difficult to progress through Portal than expert players. There were differences in times to completion, puzzle comprehension, and assessment of game mechanics when comparing novice and expert players. A continuum of players emerged between those with less gameplay expertise and those with significant gameplay expertise. There were considerable barriers to entry for novice players.