Micro-mechanical sensor for the spectral decomposition of acoustic signals

An array of electret-biased frequency-selective resonant microelectromechanical system (MEMS) acoustic sensors was proposed to perform analysis of stress pulses created during an impact between two materials. This analysis allowed classification of the stiffness of the materials involved in the impact without applying post-impact signal processing. Arrays of resonant MEMS sensors provided filtering of the incident stress pulse and subsequent binning of time-domain waveforms into frequency-based spectra. Results indicated that different impact conditions and materials yielded different spectral characteristics. These characteristics, as well as the resulting sensor array responses, are discussed and applied to impact classification. Each individual sensor element in the array was biased by an in situ charged electret film. A microplasma discharge apparatus embedded within the microsensor allowed charging of the electret film after all device fabrication was complete. This enabled electret film integration using high-temperature surface micromachining processes that would typically lead to discharge of traditionally formed electret materials. This also eliminated the traditional wafer-bonding and post-fabrication assembly processes required in conventional electret integration approaches. The microplasma discharge process and resulting electret performance are discussed within the context of the MEMS acoustic sensor array.Ph.D.Committee Chair: Allen, Mark; Committee Member: Brand, Oliver; Committee Member: Michaels, Jennifer; Committee Member: Michaels, Thomas; Committee Member: Ready, Jud W

The role of cortical morphometry of functional networks in predicting age-related cognition in older adults

Over the next three decades, the 65-and-over population is projected to nearly double, increasing from 8.5% to 16.7% of the world’s total population (He, Goodkind, and Kowal, 2016). Alarmingly, despite longer life expectancies, health is not necessarily improving (He, Goodkind, and Kowal, 2016). While all organs are affected by aging, decline in the brain’s ability to function (cognitive aging) is one of the most impactful consequences of aging on day-to-day activities and one of the most common complaints of older adults (Blazer et al., 2015). In fact, in a recent survey, almost half of individuals aged 65 or older report changes in mental ability (AARP Brain Health Survey, Fall 2015). While almost all older adults acknowledge the importance of brain health, only half actually engage in activities found to be beneficial for brain health (AARP Brain Health Survey, Fall 2015). Thus, understanding individual variability in the older adult brain, both in terms of structure and function, and its relationship with cognition and age is essential (Hedden and Gabrieli 2004). Despite the well-established widespread relationships of age and cognition with cortical structure, the nature and organization of this relationship remains underspecified. In this thesis, I investigate the nature of the relationships between cortical morphometry, cognition, and age in older adults through a contemporary neuroscience lens of the brain as a system of functional networks. In chapter one, I employ a widely-used functional network architecture as the organizing principle of the cortex to investigate how the cortical morphometry of individual networks predicts cognition and mediates the age-cognition relationship in older adults (using both cortical thickness and surface area—phenotypes both implicated in relationships with cognition but not tested in the same sample of older adults). I use a machine learning and cross-validation prediction framework to compare the predictive ability of cortical morphometry of individual functional networks to age-related cognitive abilities (declarative memory and executive function). In a second set of analyses, I apply a novel inferential test to exploratory, whole brain analyses. Specifically, I examine the number of significant point-by-point regional associations within functional networks, providing a test of the spatial extent of each functional network’s relationship with age-related cognitive abilities (compared to chance). Ultimately, making impactful theoretical and practical contributions to the field requires assessing the reproducibility and generalizability of conclusions derived from data-driven techniques. Thus, in chapter 2, I test if regions robustly associated with cognitive ability (executive function) discovered in chapter 1 and regions associated with cognitive task performance discovered in a previous study (Sun et al., 2016) predict well-established cognitive reference abilities in an independent sample of older adults. General patterns of functional connectivity (i.e., group-average functional networks) across a population(s), such as the one used in Chapter 1, provide a picture of the common functional architecture and distinct functional networks across the cortex of healthy adults (i.e., Yeo et al., 2011). These group-based networks of the functional connectome were used to assess the importance of cortical structure of functional networks in Chapter 1. However, this ignores individual differences in the integrity of these functional networks and how these individual differences relate to individual differences in cortical structure. If functional connectivity causes (or is caused by) differences in mechanisms marked by cortical structure or vice versa (e.g., individual variability in older adults’ cortical thickness may be indexing the number of synapses or intracortical myelin important for connectivity between regions as is theorized in previous studies; see Fjell et al., 2015), one would expect the two to be related and share overlapping variance in their relationship with age and cognition. Thus, in chapter 3, I examine whether individual differences in functional connectivity mediates the relationship of cortical structure with age and cognitive ability (as the relationship of structure with cognition emerges as a result of the functional system measured by functional connectivity)

Examining the role of reasoning and working memory in predicting casual game performance across extended gameplay

The variety and availability of casual video games presents an exciting opportunity for applications such as cognitive training. Casual games have been associated with fluid abilities such as working memory (WM) and reasoning, but the importance of these cognitive constructs in predicting performance may change across extended gameplay and vary with game structure. The current investigation examined the relationship between cognitive abilities and casual game performance over time by analyzing first and final session performance over 4-5 weeks of game play. We focused on two groups of subjects who played different types of casual games previously shown to relate to WM and reasoning when played for a single session: 1) puzzle-based games played adaptively across sessions and 2) speeded switching games played non-adaptively across sessions. Reasoning uniquely predicted first session casual game scores for both groups and accounted for much of the relationship with WM. Furthermore, over time, WM became uniquely important for predicting casual game performance for the adaptive games but not for the non-adaptive games. These results extend the burgeoning literature on cognitive abilities involved in video games by elucidating the differential relationships of fluid abilities across game type and extended play. More broadly, the current study illustrates the usefulness of using multiple cognitive measures in predicting performance and provides potential directions for game-based cognitive training research

Allele-specific endogenous tagging and quantitative analysis of β-catenin in colorectal cancer cells

Wnt signaling plays important roles in development, homeostasis, and tumorigenesis. Mutations in β-catenin that activate Wnt signaling have been found in colorectal and hepatocellular carcinomas. However, the dynamics of wild-type and mutant forms of β-catenin are not fully understood. Here, we genome-engineered fluorescently tagged alleles of endogenous β-catenin in a colorectal cancer cell line. Wild-type and oncogenic mutant alleles were tagged with different fluorescent proteins, enabling the analysis of both variants in the same cell. We analyzed the properties of both β-catenin alleles using immunoprecipitation, immunofluorescence, and fluorescence correlation spectroscopy approaches, revealing distinctly different biophysical properties. In addition, activation of Wnt signaling by treatment with a GSK3β inhibitor or a truncating APC mutation modulated the wild-type allele to mimic the properties of the mutant β-catenin allele. The one-step tagging strategy demonstrates how genome engineering can be employed for the parallel functional analysis of different genetic variants

Clustering phenotype populations by genome-wide RNAi and multiparametric imaging

How to predict gene function from phenotypic cues is a longstanding question in biology.Using quantitative multiparametric imaging, RNAi-mediated cell phenotypes were measured on a genome-wide scale.On the basis of phenotypic ‘neighbourhoods', we identified previously uncharacterized human genes as mediators of the DNA damage response pathway and the maintenance of genomic integrity.The phenotypic map is provided as an online resource at http://www.cellmorph.org for discovering further functional relationships for a broad spectrum of biological modul

Gross and net production during the spring bloom along the Western Antarctic Peninsula

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of New Phytologist Trust for personal use, not for redistribution. The definitive version was published in New Phytologist 205 (2015): 182-191, doi:10.1111/nph.13125.This study explores some of the physiological mechanisms responsible for high productivity near the shelf in the Western Antarctic Peninsula despite a short growing season and cold temperature. We measured gross and net primary production at Palmer Station during the summer 2012/2013 via three different techniques: 1) incubation with H218O; 2) incubation with 14CO2; and 3) in situ measurements of O2/Ar and triple oxygen isotope. Additional laboratory experiments were performed with the psychrophilic diatom Fragilariopsis cylindrus. During the spring bloom, which accounted for more than half of the seasonal gross production at Palmer Station, the ratio of net to gross production reached a maximum greater than ~60%, among the highest ever reported. The use of multiple-techniques showed that these high ratios resulted from low heterotrophic respiration and very low daylight autotrophic respiration. Laboratory experiments revealed a similar ratio of net to gross O2 production in F.cylindrus and provided the first experimental evidence for an important level of cyclic electron flow (CEF) in this organism. The low ratio of community respiration to gross primary production observed during the bloom at Palmer Station may be characteristic of high latitude coastal ecosystems and partially supported by a very active CEF in psychrophilic phytoplankton.This study was supported by funds from the US National Science Foundation (Award numbers 1040965 and 1043593). Funding to PDT was provided by the Natural Science and Engineering Research Council of Canada

Bodies, technologies and action possibilities: when is an affordance?

Borrowed from ecological psychology, the concept of affordances is often said to offer the social study of technology a means of re-framing the question of what is, and what is not, ‘social’ about technological artefacts. The concept, many argue, enables us to chart a safe course between the perils of technological determinism and social constructivism. This article questions the sociological adequacy of the concept as conventionally deployed. Drawing on ethnographic work on the ways technological artefacts engage, and are engaged by, disabled bodies, we propose that the ‘affordances’ of technological objects are not reducible to their material constitution but are inextricably bound up with specific, historically situated modes of engagement and ways of life

eGFP-tagged Wnt-3a enables functional analysis of Wnt trafficking and signaling and kinetic assessment of Wnt binding to full-length Frizzled

The Wingless/Int1 (Wnt) signaling system plays multiple, essential roles in embryonic development, tissue homeostasis and human diseases. Although many of the underlying signaling mechanisms are becoming clearer, the binding mode, kinetics and selectivity of 19 mammalian WNTs to their receptors of the class Frizzled (FZD$_{1-10}$) remain obscure. Attempts to investigate Wnt-FZD interactions are hampered by the difficulties in working with Wnt proteins and their recalcitrance to epitope tagging. Here, we used a fluorescently tagged version of mouse Wnt-3a for studying Wnt-FZD interactions. We observed that the enhanced GFP (eGFP) tagged Wnt-3a maintains properties akin to wild-type Wnt-3a in several biologically relevant contexts. The eGFP-tagged Wnt-3a was secreted in an evenness interrupted (EVI)/Wntless-dependent manner, activated Wnt/β-catenin signaling in 2D and 3D cell culture experiments, promoted axis duplication in Xenopus embryos, stimulated LDL receptor–related protein 6 (LRP6) phosphorylation in cells and associated with exosomes. Further, we used conditioned medium containing eGFP-Wnt-3a to visualize its binding to FZD and to quantify Wnt-FZD interactions in real time in live cells, utilizing a recently established NanoBRET-based ligand binding assay. In summary, the development of a biologically active, fluorescent Wnt-3a reported here opens up the technical possibilities to unravel the intricate biology of Wnt signaling and Wnt-receptor selectivity