Browsing by Author "Hoke, Kim, committee member"
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Item Embargo An investigation of synaptic vesicle docking and priming and a proposed method for quantitatively measuring both in Drosophila using electron tomography(Colorado State University. Libraries, 2023) Twiggs, Jasmin A., author; Reist, Noreen, advisor; Hoerndli, Frederic, committee member; Hoke, Kim, committee member; Tamkun, Michael, committee memberThe nervous system, as the body's command center, plays a crucial role in cellular communication within the brain and between the brain and other body systems. Neurons, the individual cellular units, transmit electrical information and communicate with other cells through neurotransmitter release in response to electrical stimuli. Chapter 1 introduces the foundational concepts of neuronal structure and function and delves into the mechanisms underlying neurotransmitter release. Special attention is given to the neuromuscular junction (NMJ), a well-studied chemical synapse crucial for muscle movement. The synaptic vesicle cycle is introduced, with particular emphasis on docking and priming. The significance of active zones, specialized sites for efficient signal transmission, and their associated structural components are underscored. Synaptotagmin, a pivotal protein in calcium-triggered vesicle fusion, is discussed with emphasis on its C2B polylysine motif. Throughout the chapter, the utility of Drosophila as a model system for studying synaptic processes, particularly at the NMJ, is emphasized. In sum, Chapter 1 provides the foundational knowledge essential for comprehending the intricate cellular and molecular facets of synaptic communication within the nervous system, serving as a precursor to subsequent chapters' investigations. Chapter 2 examines synaptotagmin's C2B polylysine motif and its role in synaptic vesicle docking at the Drosophila NMJ. It explores the polylysine motif's potential involvement in endocytosis, demonstrates an unaffected interaction with AP-2, and uses electron microscopy to find no significant changes in vesicle distribution. The findings suggest that the reduced neurotransmitter release in the polylysine mutant is likely due to an impairment in vesicle priming. Chapter 3 introduces a method for studying synaptic vesicle docking and priming in Drosophila, using electron tomography. I address the limitations of conventional electron microscopy and underscore the need for higher-resolution techniques to assess molecular structures that mediate physiological processes. Chapter 3 also emphasizes the significance of the contact area between docked vesicles and the presynaptic membrane as a correlate of vesicle priming. The protocol, expected results, and key considerations are discussed. The methods presented in Chapter 3 offer a promising approach for understanding synaptic processes. In Chapter 4, I discuss key considerations for when standard electron microscopy can be used for assessing vesicle docking. Then, I discuss how the electron tomography method presented in Chapter 3 could not only confirm the results found in Chapter 2, that the synaptotagmin C2B polylysine motif is not implicated in vesicle docking but could also be used to directly test the mutant's role in priming. Specific aims for future studies on the synaptotagmin polylysine mutation in Drosophila are presented, potential results and interpretations are discussed. Finally, I showcase interesting, unpublished findings from electron tomograms I have taken at the Drosophila NMJ and discuss their potential significance.Item Open Access Cuticular hydrocarbons as modulators of social interactions in honeybee colonies(Colorado State University. Libraries, 2011) Scholl, Jacob, author; Naug, Dhruba, advisor; Ode, Paul, committee member; Hoke, Kim, committee memberHoneybees are known for their highly complex social organization with individuals of different ages working in a coordinated manner to ensure colony functionality. While local-level inter-individual interactions are critical in transferring global-level information about colony needs, these same interactions are also exploited by various pathogens to spread themselves within the colony. It is therefore important to understand the proximate mechanisms that generate the exact structure of the interaction network within the colony. While bees of different ages possess unique cuticular hydrocarbon (CHC) profiles providing a potential basis for mediating these interactions, it is not entirely clear whether these odor cues in fact play a role in organizing the interaction network among them. The first part of my thesis examines the CHC profiles of bees of different ages and how their neuronal sensitivity to these odors enable them to discriminate each other and generate the observed interaction network in the colony. Using behavioral observations to quantify the interaction frequencies between different age groups and using electroantennograms to determine the olfactory sensitivity of each age to the odor of every other age, I determined the correlation between the two. The results show that young bees are indiscriminant in their interactions, which matches their lack of olfactory bias toward any age-specific odor, while old bees interact mostly with bees of a similar age, which corresponds with their higher olfactory sensitivity to the odor of such bees. Age-based differences in both cuticular hydrocarbons and the olfactory sensitivity to them thus provide a mechanistic basis to the observed interaction structure in the colony and suggests that an active behavioral segregation is the primary mechanisms that generates the organizational immunity in the colony, shielding the younger bees from interacting with older bees who are also more likely to be infected with pathogens. The second part of my thesis examines if the energetic stress related to a pathogenic infection can alter the hydrocarbon profiles of individuals and lead to changes in the interaction network within the colony. Using gas chromatography, I was able to show that energetic state of an individual has a significant influence on its CHC profile. Following this, using a choice test where subjects at different energetic states were made to choose between chemical mimics of starved and satiated bees in a y-maze, I demonstrated that both fed and starved bees preferred to interact with recipients that are at similar energetic states. While this is somewhat surprising, a cost-benefit analysis showed how the decision to donate food is a function of both the energetic state of the receiver as well as the donor. While the benefit to cost ratio is positive for a depleted donor to donate to a starved recipient, this ratio is not positive for a fed donor to donate to the same starved recipient. This suggests that energetic stress, by changing the CHC profiles of individuals, can lead to social interactions being restricted between individuals of similar energetic states. Since the energetic state of an individual is likely to be correlated with its infection status, this has the potential to generate a behavioral segregation between uninfected and infected individuals and help maintain the organizational immunity of the colony. My thesis research therefore establishes the role of age- and condition-dependent olfactory cues in organizing the interaction network within the colony and its implications for disease dynamics.Item Open Access Expanding on expansion: genome gigantism and its effects on DNA methylation, RNA splicing and organellar scaling(Colorado State University. Libraries, 2023) Adams, Alexander Nichols, author; Mueller, Rachel, advisor; Hanson, Jeffrey, committee member; Hoke, Kim, committee member; Sloan, Dan, committee memberAcross the tree of life, the correlated traits of genome size and cell size both vary by orders of magnitude, with the increase in genome size being largely attributable to an increase in transposable elements (TEs) throughout the genome. This accumulation of TEs affects many facets of the cell including DNA regulation, organellar scaling, and RNA transcription. This dissertation will explore all 3 of these facets through the lens of genome gigantism and address how these facets differ in large cells in comparison to cells that are more typical in size. The first chapter will discuss methylation of cytosines at genomic CpG dinucleotide sites that silence TEs. TE abundance drives differences in genome size, but TE silencing variation across genomes of different sizes remains largely unexplored. Salamanders include most of the largest C-values — 9 to 120 Gb. We measured CpG methylation levels in salamanders with genomes ranging from 2N = ~58 Gb to 4N = ~116 Gb. We compared these levels to results from endo- and ectothermic vertebrates with more typical genomes. Salamander methylation levels are ~90%, higher than all endotherms. However, salamander methylation does not differ from the other ectotherms, despite a ~100-fold difference in nuclear DNA content. Because methylation affects the nucleotide compositional landscape through 5-methylcytosine deamination to thymine, we quantified salamander CpG dinucleotide levels and compared them to other vertebrates. Salamanders have comparable CpG levels to other ectotherms, and ectotherm levels are higher than endotherms. These data show no shift in global methylation at the base of salamanders, despite a dramatic increase in TE load and genome size. This result is reconcilable with previous studies by considering endothermy and ectothermy, which may be more important drivers of methylation in vertebrates than genome size. The next chapter will look at how an increase in cell size affects organellar structure and abundance. Depending on their shape, organelles can scale in larger cells by increasing volume, length, or number. Scaling may also reflect demands placed on organelles by increased cell size. The 8,653 species of amphibians exhibit diverse cell sizes, providing a powerful system to investigate organellar scaling. Using transmission electron microscopy and stereology, we analyzed three frog and salamander species whose enterocyte cell volumes range from 228 to 10,593 μm3. We show that the nucleus increases in radius (i.e. spherical volume) while the mitochondria increase in total network length; the endoplasmic reticulum and Golgi apparatus, with their complex shapes, are intermediate. Notably, all four organelles increase in volume proportionate to cell volume. This pattern suggests that protein concentrations are the same across amphibian species that differ 50-fold in cell size, and that organellar building blocks are incorporated into more or larger organelles following the same "rules" across cell sizes, despite variation in metabolic and transport demands. This conclusion contradicts results from experimental cell size increases, which produce severe proteome dilution. We hypothesize that salamanders have evolved the biosynthetic capacity to maintain a functional proteome despite a huge cell volume. Finally, the last chapter will be discussing differences in intronic splicing, an important step that pre-mRNA transcripts undergo during processing in the nucleus to become mature mRNAs. Although long thought to occur exclusively in a single step, some introns are now also known to be removed in multiple steps through a process called recursive splicing. This non-canonical form of splicing is hypothesized to aid with intron splicing fidelity, particularly in longer introns. Using West African lungfish (Protopterus annectens; genome size ~40Gb) as a model, we use total RNA-seq data to test the hypothesis that gigantic genomes, which have relatively long introns, have increased levels of recursive splicing compared to genomes of more typical size. Our results reveal levels of recursive splicing at conserved sites similar to those seen in humans, suggesting that genome-wide intronic expansion accompanying evolutionary increase in genome size is not associated with the evolution of high levels of recursive splicing. However, in addition to these results, we also observed patterns of decreasing RNA-seq read depths across entire intron lengths and note that both canonical co-transcriptional splicing and stochastic recursive splicing using many random splice sites could produce this pattern. Thus, we infer canonical co-transcriptional splicing and/or stochastic recursive splicing — but not widespread recursive splicing at conserved sites — manage the removal of long introns.Item Open Access Learning and decision making along a nutritional gradient(Colorado State University. Libraries, 2019) Katz, Keziah, author; Naug, Dhruba, advisor; Hoke, Kim, committee member; Kondratieff, Boris, committee member; Pratt, Stephen, committee memberNutrition is fundamental to the life history of all animals and the behavioral processes by which animals acquire nutrition are of central interest to students of animal behavior. How an animal learns about available food resources, and the strategies adopted to acquire food resources are therefore of central importance. While animal nutrition is quite complex, energy is a fundamental nutrient and is the focus of this work. In chapter 1, honeybees were fed or starved before they were given a choice assay to determine how individual energetic state altered their choice between gathering information about food resources and consuming known food resources. It was found that bees which were relatively satiated prioritized the collection of information over energy. This work was expanded in chapter 2, in which the energetic states of honeybee colonies were manipulated, in addition to the manipulation of individual energetic state. This experiment provided insights into how group members make decisions in the presence of conflicting individual and group level interests and found that honeybee behavioral phenotypes vary in how they prioritize group and individual needs. The first two chapters focus on how animals make decisions after they have acquired some information, but differences in learning also play a vital role in the acquisition of nutrition. In chapter 3, bees were weighed early and late in their lifetimes, and it was found that bees with more stable weight percentile ranks performed better in a learning assay than bees with unstable weight percentile ranks. As nutritional environment plays a significant role on the body weight of individuals, this may indicate that consistent nutritional conditions contribute to bee cognition. Along with nutrition, body weight is also correlated with the metabolic rate of individuals. Metabolic rate is directly tied to the energy acquisition behavior of animals, as it determines how and at what rate energy is processed by an animal. In order to evaluate how metabolic rate alone influences nutrient acquisition, a model, presented in Chapter 4, was constructed that evaluated the performance of different metabolic rates in different nutritional environments. In general, high metabolic rates were more favorable in rich nutritional environments and low metabolic rates were more favorable in poor nutritional environments. It was also shown that diversity of metabolic rates within a group is advantageous in some environments. Taken together, this work indicates that nutrition, in the form of energy, plays a vital role in the how animals learn and make decisions. This is true for nutrition at both the individual and group level, over immediate and long-term timescales, and for physiological differences in the capacity of an animal to assimilate energy. These findings have broad implications in behavioral ecology and are discussed in terms of optimal foraging, group behavior, developmental plasticity, and gene-environment interactions.Item Open Access Linking organismal physiology and the landscape to predict vulnerability to climate change(Colorado State University. Libraries, 2023) Cicchino, Amanda Stephanie, author; Funk, W. Chris, advisor; Ghalambor, Cameron, committee member; Kanno, Yoichiro, committee member; Hoke, Kim, committee member; Landguth, Erin, committee memberGlobal temperatures continue to increase at unprecedented rates, both in mean and in variance. Thus, a major challenge for scientists of the 21st century is to predict whether species will persist through these changes. One way to partly assess vulnerability to climate change is to investigate the relationships between the environment and traits that are either particularly sensitive to temperature or may confer resilience against thermal changes. In ectotherms, external temperatures dictate their physiology, thus thermal physiological traits may be key to understanding ectothermic persistence. Although population variation is integral to the evolvability of thermal physiological traits, most studies using these traits to infer vulnerability extrapolate data from one or few populations to represent the species. Furthermore, many studies also use coarse metrics of environmental temperatures which may not fully capture the variation experienced by the organism. Here, using a cold-water frog system, I demonstrate the relationships between thermal physiological traits and local environmental temperatures among populations. In my first chapter, I provide a brief overview of ectothermic physiology, environmental thermal landscapes, and the ecology of the two species of tailed frogs that I investigated. In my second chapter, I show that populations of tailed frogs vary in their critical thermal limit (CTmax) plasticity, which impacts species-level assessments of vulnerability. I also demonstrate the methodological impacts of ignoring acute responses to temperature when estimating plasticity in this trait. For my third chapter, I demonstrate relationships between CTmax and local thermal environments, including temporal and spatial variability in temperature, among populations of tailed frogs. These results show that tailed frogs have limited opportunity for behavioural avoidance of warm temperatures, and that populations of one tailed frog species show a positive relationship between CTmax and maximum stream temperature while populations of the other species does not. In my fourth chapter, I test the critical assumption that CTmax is related to fitness, specifically mortality in ecologically relevant temperatures. My results show that populations with higher estimates of CTmax experience less mortality from thermal stress in temperatures experienced in nature, demonstrating the link between CTmax and fitness. Lastly, in my fifth chapter, I return to the plasticity in CTmax results and demonstrate the relationship between this trait and local thermal environments, showing that populations experiencing greater temperature fluctuations have greater estimates of plasticity in CTmax. Overall, these results underscore the importance of sampling widely among populations when inferring vulnerability to climate changes from physiological traits. The population variation in CTmax and its plasticity that I uncovered demonstrate the differing trends in vulnerability to climate change for the two species investigated. This work also highlights the importance of quantifying local thermalscapes and highlight how similar environments can differentially shape physiological tolerance and patterns of vulnerability among populations, in turn impacting vulnerability to future warming.Item Open Access Living in the slow or fast lane: cognitive phenotypes in honeybees(Colorado State University. Libraries, 2021) Tait, Catherine A., author; Naug, Dhruba, advisor; Hoke, Kim, committee member; Ode, Paul, committee member; Brockmann, Axel, committee memberThe evolution and maintenance of cognitive variation is a question of fundamental interest in animal behavior because differences in cognition are predicted to underlie differences in behavior. The correlation between behavioral and cognitive variation has largely been conceptualized in terms of the speed-accuracy trade-off driving alternative cognitive strategies where 'fast' individuals are superficial learners that make inaccurate, risk-prone decisions relative to 'slow' individuals. My research has explored the factors that select for different cognitive abilities across species and the mechanisms that maintain variation in cognitive ability within species. To address these questions, I have identified how individuals of four honeybee species (Apis mellifera, A. cerana, A. dorsata, A. florea) differ in performance on multiple cognitive tasks and explored how such variation translates to behavioral outcomes and is shaped by ecology. In chapter one, I tested for the presence of variation in two different learning abilities in honeybee foragers and whether any component of learning influenced wing damage, an indicator of survival. My results demonstrated considerable interindividual variation in different types of learning abilities such that landmark and olfactory learning were negatively correlated. Additionally, I found that olfactory learning was positively correlated with maneuverability performance during flight, a measure which in turn positively influenced wing damage, a proxy for survival. This experiment demonstrated that individuals differ considerably in how they perform on two cognitive tasks and that cognitive ability has important implications for behaviors associated with survival. This work was further explored in chapter 2, where I studied how differences in learning preference relate to decision making during foraging. I measured individual latency to learn on a solitary foraging task and latency to learn on a social foraging task and found that individuals that perform well in a solitary learning task perform poorly in a social learning task. These findings suggest that honeybees specialize in one type of learning strategy when making foraging decisions, and such differences may have important implications for how individuals provision their colony. The first two chapters focused on how differences in performance on cognitive tasks may represent a trade-off that correlates to different behaviors. In the latter half of my dissertation, I first used multiple cognitive traits to define a cognitive phenotype in an individual and then investigated how such differences might impact performance on multiple behaviors and life history traits to determine functional consequences of cognitive variation. I then expanded this research to determine how differences in ecology shape cognitive phenotypes. In chapter three, I tested for the presence of distinct cognitive phenotypes in A. mellifera foragers by measuring multiple cognitive traits and determining whether these traits covary to produce distinct slow and fast cognitive phenotypes. I then compared performance on multiple behavioral and life history tasks to see if there were functional differences between these cognitive types. My results indicate the presence of two cognitive phenotypes that meet the predictions of the speed-accuracy trade-off and that are conserved across colonies. Compared to slow bees, fast bees were described by high associative learning, high preference for novelty and high preference for variance, bees which also engage in more nursing behavior and transition to becoming a forager at an earlier age. In chapter four, which explored how ecological and life history differences shape cognitive phenotypes between closely related honeybee species, I tested for differences in the cognitive phenotype in four honeybee species, each of which occupied a unique ecological niche that was correlated to their position on the slow-fast life history axis. My results indicate that a set of cognitive traits consistently covary within each species, resulting in slow and fast cognitive phenotypes that meet the predictions of the speed-accuracy tradeoff. I also found that the four species do not align on a slow-fast cognitive axis due to known differences in their life history and nesting ecology. Rather, cognitive differences among the species appear correlated to their brain size, which may be driven by differences in foraging range. Taken together, this work indicates that cognitive variation at the individual level has important behavioral and life history outcomes that may impact how the individual interacts with their environment and how the colony performs. At the species level, cognitive variation appears to be driven by a complex relationship with the species unique environment as well as underlying trade-offs associated with costs of cognition.Item Open Access S-nitrosylation mediates synaptic plasticity in the retina(Colorado State University. Libraries, 2015) Tooker, Ryan E., author; Vigh, Jozsef, advisor; Tamkun, Michael, committee member; Hentges, Shane, committee member; Hoke, Kim, committee memberOver the course of an entire day, our visual system must accommodate intensities of light that can change by a factor of 10¹⁰. In order to do so, the retina adapts to large, daily changes in natural light intensity by shifting its dynamic range of coding. For example, as morning light intensity increases, the retina implements multiple strategies that result in decreases in overall sensitivity in order to avoid saturation. However, adaptation to bright environments poses the inherent risk of losing visual information carried by dim/weak signals in complex natural scenes. Here we studied whether the light-evoked increase in retinal nitric oxide (NO) production is followed by NO-mediated, direct post-translational modification of proteins called S-nitrosylation and if it contributes to the modulation of the dynamic range of vision. In the central nervous system, including the retina, S-nitrosylation has not been considered to be significant under physiological conditions, and instead, has been primarily associated with neurodegenerative diseases. In this study, we provide immunohistochemical and proteomic evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner. Functionally, we report a novel form of activity-dependent synaptic plasticity via S-nitrosylation: a “weighted potentiation” that selectively increases the output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input-output ratio for strong stimuli unaffected. Importantly, the NO action resulted in a weighted potentiation of Mb output in response to small (≤-30 mV) depolarizations. Our data strongly suggest that in the retina, light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant post-translational modification affecting a wide range of proteins under physiological conditions. S-nitrosylation may function to extend the dynamic range of vision by counteracting the decreases in retinal sensitivity during light adaptation ultimately preventing the loss of visual information carried by dim scotopic signals. Finally, our results may set the framework for exploring the role of S-nitrosylation in certain neurodegenerative retinal diseases that are associated with toxic levels of NO.Item Open Access Sex-specific cardiometabolic responses to chronic stress and the impact of prefrontal-medullary regulation(Colorado State University. Libraries, 2024) Dearing, Carley, author; Myers, Brent, advisor; Smith, Bret, committee member; Fails, Anna, committee member; Hoke, Kim, committee memberGlobally, cardiovascular and metabolic disease are leading causes of death and years lived with disability. Chronic stress is an etiologic factor in both diseases and biologic sex plays an important role in the progression and prognosis of each. However, the neurobiological basis of how chronic stress exposure intersects with sex, cardiovascular, and metabolic function to impact systemic physiology is poorly understood. Prior studies from our group indicate that, in rats, the prefrontal infralimbic cortex (IL)-rostral ventrolateral medulla (RVLM) circuit inhibits sympathetic and endocrine responses to stress. Therefore, we aimed to address the overarching hypothesis that the IL-RVLM circuit is necessary for homeostatic function and mitigation of deleterious changes to metabolic, cardiac, and microvascular function following chronic stress. To this end, an intersectional genetic approach was used to induce Cre-dependent expression of tetanus toxin light chain and inhibit neurotransmitter release from RVLM-projecting IL neurons in male and female rats. Rats were then exposed to 2 weeks of chronic variable stress (CVS). Metabolic function was assessed with a fasted glucose tolerance test. Cardiovascular function was examined with echocardiography and non-invasive hemodynamics. Additionally, microvascular function was quantified via ex-vivo resistance arteriole pressure myography. Our results indicate that glucose tolerance, left ventricular structure, and vascular function are all impacted in a sex-dependent manner. Following chronic stress, circuit-intact females show glucodysregulation characterized by decreased glucose clearance, elevated corticosterone, and insulin insensitivity. Regardless of stress, circuit inhibition in females also impaired glucoregulation but was characterized by elevated glucagon with no compensatory insulin response. Circuit inhibition also increased relative heart size, increased endothelial-dependent vasodilation at both normotensive and hypertensive pressures, and increased myogenic tone and diastolic wall strain. These changes indicate that chronic stress in females leads to broad endocrine-autonomic dysregulation of glucose homeostasis and microvascular function that is exacerbated by IL-RVLM inhibition. While chronic stress in males resulted in an adaptive metabolic response and no changes in normotensive vasodilation, circuit inhibition in chronically-stressed males lead to glucodysregulation and increased endothelial-dependent vasodilation at hypertensive pressures. Additionally, these animals had reduced ventricular wall thickness in diastole. Broadly, these results support the hypothesis that the IL-RVLM circuit is necessary for appropriate glucose homeostasis and vascular function and that circuit inhibition and chronic stress lead to sex-specific responses that may differentially impact the progression of cardiovascular and metabolic disease.Item Open Access Slow and noisy: developmental time and gene expression kinetics in big cells(Colorado State University. Libraries, 2023) Taylor, Alexandra, author; Mueller, Rachel, advisor; Prasad, Ashok, advisor; Hoke, Kim, committee member; Krapf, Diego, committee memberEvolutionary increases in genome size, cell volume, and nuclear volume have been observed across the tree of life, with positive correlations documented between all three traits. It is well documented that developmental tempo slows as genomes, nuclei, and cells increase in size, yet the driving mechanisms are poorly understood. Meanwhile, the dramatic increases in cell volume seen across the tree of life pose interesting questions about a potential relationship between cell volume and stochastic noise at the single cell level, but this remains an underexplored area of research. To bridge these knowledge gaps, we use a mix of deterministic and stochastic, as well as species-specific and more general, models of the somitogenesis clock. In doing so, we explore the impact of changing intra-cellular gene expression kinetics induced by increasing genome size, nuclear volume, and cell volume on developmental tempo and gene expression noise. Results suggest that longer transcriptional and nuclear export times act to slow cell and developmental processes down as genome size and cell volume increase, and that "search processes" undergone by gene products within a cell become noisier with increasing volume. Analyses of stochastic model simulations and existing empirical data bring into question whether or not cell-autonomous oscillations can truly exist in the absence of cell-to-cell signaling.Item Unknown Some topics in high-dimensional robust inference and graphical modeling(Colorado State University. Libraries, 2021) Song, Youngseok, author; Zhou, Wen, advisor; Breidt, Jay, committee member; Cooley, Dan, committee member; Hoke, Kim, committee memberIn this dissertation, we focus on large-scale robust inference and high-dimensional graphical modeling. Especially, we study three problems: a large-scale inference method by a tail-robust regression, model specification tests for dependence structure of Gaussian Markov random fields, and a robust Gaussian graph estimation. First of all, we consider the problem of simultaneously testing a large number of general linear hypotheses, encompassing covariate-effect analysis, analysis of variance, and model comparisons. The new challenge that comes along with the overwhelmingly large number of tests is the ubiquitous presence of heavy-tailed and/or highly skewed measurement noise, which is the main reason for the failure of conventional least squares based methods. The new testing procedure is built on data-adaptive Huber regression, and a new covariance estimator of the regression estimate. Under mild conditions, we show that the proposed methods produce consistent estimates of the false discovery proportion. Extensive numerical experiments, along with an empirical study on quantitative linguistics, demonstrate the advantage of our proposal compared to many state-of-the-art methods when the data are generated from heavy-tailed and/or skewed distributions. In the next chapter, we focus on the Gaussian Markov random fields (GMRFs) and, by utilizing the connection between GMRFs and precision matrices, we propose an easily implemented procedure to assess the spatial structures modeled by GMRFs based on spatio-temporal observations. The new procedure is flexible to assess a variety of structures including the isotropic and directional dependence as well as the Matern class. A comprehensive simulation study has been conducted to demonstrate the finite sample performance of the procedure. Motivated from the efforts on modeling flu spread across the United States, we also apply our method to the Google Flu Trend data and report some very interesting epidemiological findings. Finally, we propose a high-dimensional precision matrix estimation method via nodewise distributionally robust regressions. The distributionally robust regression with an ambiguity set defined by Wasserstein-2 ball has a computationally tractable dual formulation, which is linked to square-root regressions. We propose an iterative algorithm that has a substantial advantage in terms of computation time. Extensive numerical experiments study the performance of the proposed method under various precision matrix structures and contamination models.Item Unknown The experience of novelty: another dimension to subjective memory experience?(Colorado State University. Libraries, 2014) Staley, Shelly, author; Cleary, Anne, advisor; Seger, Carol, committee member; Hoke, Kim, committee memberSubjective experiences of memory (e.g., feelings of familiarity) have been a topic of much research. Though novelty might be considered a manifestation of memory (insofar as some form of memory for the past is required in order for novelty recognition or detection to occur), subjective experiences of novelty have largely been ignored in the current memory literature. The present study used a rating scale to measure the subjective feeling of novelty. One goal was to investigate potential mechanisms of feelings of novelty. Another was to determine how feelings of novelty relate to feelings of familiarity; for example, many models assume that novelty is simply the inverse of familiarity. Two experiments reported here examined if this presumed relationship between familiarity and novelty is an accurate assumption. In one experiment, subjects viewed words in a study list and then were tested on cues that potentially shared orthographic features with the study words while duration of cue-prime exposure and cue-match-priming effects were observed. In another, subjects were tested after having repeated the test cues aloud either once or 30 times. Both experiments compared a familiarity rating scale with a novelty rating scale. No effects of duration of exposure (either through priming in Experiments 1 and 2 or repetitions in Experiment 3) were observed, helping to rule out several potential mechanisms of feelings of novelty. Differences in how familiarity ratings and novelty ratings responded to the experimental manipulations were found in both experiments, suggesting that the sense of novelty is not simply the inverse of familiarity.Item Unknown Undermining learning: the impact of rewards on learning behavior(Colorado State University. Libraries, 2016) Wehe, Hillary, author; Seger, Carol, advisor; Rhodes, Matthew, committee member; Conner, Bradley, committee member; Hoke, Kim, committee memberThe undermining effect suggests that external rewards can decrease levels of internal motivation. Research exploring student motivation shows that internally motivated students appear to engage longer and in more challenging tasks compared to students focused on external rewards or performance feedback. The current study tested variables that may decrease susceptibility to motivational undermining for learning behaviors. In all studies, students were assigned to either a reward or non-reward condition and completed a word-learning task followed by a final test. Subjects were given the option to choose to re-study the words at two times during the task—pre- (while reward is still achievable) and post-test (after reward is given and no further extrinsic reward is achievable). Across all studies, an undermining effect was expected: Non-reward subjects would spend a greater amount of time reviewing the words during the post-test interval compared to the reward group. Study 1 directly tested the hypothesis by observing whether or not the reward groups behaved differentially at the pre- and post-test choice. Reward subjects spent significantly less time engaging in the task during the post-test review phase, supporting the presence of the undermining effect (t (1,60)=2.06, p = .02, 1-tailed) but a 2 (group: reward x non-reward) x 2 (study time: pre-test x post-test) repeated measures ANOVA comparing the mean study times for the reward and non-reward subjects’ pre-test study and post-test review time revealed that the interaction between group and study time did not reach significance (F (1,60) = 3.52, p = .065). Study 2 was identical to the first study but with the addition of a surprise, 24-hour delayed memory test to examine whether the extra post-test study had beneficial effects on long-term retrieval. Non-reward subjects were hypothesized to recall more items on a delayed memory test compared to reward subjects due to increased study time. A 2 (group: reward x non-reward) x 2 (study time: pre-test x post-test) repeated measures ANOVA was conducted to compare the mean study times for the reward and non-reward subjects’ pre-test study and post-test review times. The interaction between group and time spent on task was significant (F (1,241) = 4.24, p < .05) but there was not a significant main effect for the between subjects variable of reward on the amount of time spent engaging in the task during the pre- and post-test phases (F (1)= .63, p = .44). A 2 (group: reward vs. non-reward group) x 2 (test performance: immediate x delayed) repeated measures ANOVA was conducted to compare the average accuracy between groups on the delayed memory test. There was not a main effect of group on performance (F (1, 110) = .82, p = .38) and the interaction between reward group and immediate or delayed test was not significant (F (1,156) = .201, p = .65). Study 3 was similar to the first study but subjects were allowed to choose the material they were learning (i.e., Swahili or Lithuanian words). The element of choice was expected to increase the degree of control and internal motivation students experienced and consequently decrease the effect of undermining between the reward and non-reward group. Specifically, study times between the reward and non-reward group were hypothesized to be equal between groups and higher than then a forced choice condition. A 2 (group: reward x non-reward) x 2 (choice: self-determined x forced-choice) x 2 (study time: pre-test x post-test) x 2 (language: Swahili x Lithuanian) repeated measures ANOVA was conducted. The main effect of choice condition was not significant (F (1,60) = .140, p = .71). The main effect of reward was also not significant (F (1,60) = .920, p = .34) but the interaction between choice and reward on time spent on task was significant (F (1,60) =4.11, p < .05). A 2 (group: reward x non-reward) x 2 (choice: self-determined x forced-choice) repeated measures ANOVA was conducted to compare performance on an immediate memory test for the self-determined and forced choice group but the effect was non-significant (F (1,60) = .67, p = .16); in addition, there was not a significant main effect of reward (p =.32) nor was there an interaction (p = .16).