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SUPPORTING END-USERS IN PROGRAMMING ROBOT MOTIONS
No full textAs robots are adopted into a broader variety of application domains, end-users coming from a wide spectrum in terms of technical experience, physical and cognitive abilities, and professional backgrounds may need to customize robot behaviors. However, end-user robot programming of motions can be difficult, particularly for non-expert users who are not well-versed in technical aspects of robot motion. This dissertation seeks to design support mechanisms to assist end-users in programming robot motions.
Through four studies, I investigate how to support end-users in programming robot motions. In Study 1, I investigate ways to support end-users in programming robot manipulation tasks. In Study 2, I explore whether curriculum-based training for kinesthetic teaching can support end-users in learning to develop optimal programs. In Study 3, I investigate the possibilities of involving older adults in programming physical assistance in their homes and derive guidelines for designing robot programming interfaces for older end-users. In Study 4, I explore how to provide cognitive support and simulate virtual peer interactions to support older adults in programming robot assistance. Results from these studies highlight benefits to supporting end-users in programming robot motions, such as improving end-users’ task efficiency and mental models of programming systems and providing comfort and assistance when end-users face roadblocks while programming.
This dissertation contributes knowledge on how to support end-users in more easily and effectively programming robot motions. Through my investigations, I develop programming support that assists with various aspects of end-user robot programming. I explore methodological approaches for evaluating end-user robot programming systems in lab and real-world environments. Furthermore, results presented in this dissertation provide insight into factors that can contribute to or limit the effectiveness of programming support to guide further research toward making end-user robot programming more accessible. This dissertation motivates future research toward involving non-experts in the design of robot behaviors, prototyping intelligent programming support, and making robot programming more accessible beyond lab environments
Spatial transcriptomics of layer 4 of the mouse posteromedial barrel subfield reveals gradients of gene expression and differential transcriptional responses to experience dependent plasticity
No full textPast studies have demonstrated cortical region-specific gene expression patterns. Recent research on cytoarchitectonic variations and gradients of functional specialization within a cortical region, however, suggests the importance of local transcriptional variations within cortical regions. In my thesis work, I took advantage of the topographically organized mouse posteromedial barrel subfield (PMBSF), and spatially resolved transcriptomic profiling, to test the hypothesis that there exist spatial transcriptional gradients across the tangential orientation of layer 4 (L4) in the mouse PMBSF. We identified multiple tangential transcriptional gradients within L4, which were correlated with spatial location. Another focus of my thesis work is transcriptional changes in response to long-term experience dependent plasticity (EDP), which is essential for an animal’s survival in an ever-changing environment. Prior research on activity-dependent gene expression primarily focused on short-term (hours) changes. Yet long-term (days or weeks) transcriptional changes are pertinent to structural and physiological changes of neurons, and learning and adaptation of animals. Moreover, few studies have sought to determine the differential deprived and spared responses in the transcriptomes. Here we used the topographically organized mouse PMBSF L4 and spatial transcriptomics to test the hypothesis that differential transcriptional responses occur in the deprived and spared barrels following seven days of chessboard pattern whisker deprivation. Analysis of differentially used genes and gene co-regulatory networks revealed biological processes enriched in the deprived or the spared barrels, including those related to ribosome and translation, neuropeptide signaling, microglial function, and regulation of synaptic transmission
Extracting Mesoscale Neuron Anatomy from Whole-Brain Images
No full textRecent advances in brain tissue preparation and imaging have made it possible to image entire mammalian brains at sub-micron resolution. This has made it possible to capture the entire axonal projections of neurons, which can be ~10^(-1) m in length while only ~10^(-6) m in thickness. The throughput of collecting this data is scaling rapidly, making it possible to build brain-wide atlases of neuronal subtypes and connectivity patterns. However, there is a need for computational analysis pipelines that can scale to this rate of data collection.
This work describes a method that performs neuron tracing using a set of automatically generated neuron fragments. The approach leverages machine learning segmentation models while scaling to whole-brain images. Next, a novel framework is proposed to map neuron traces with diffeomorphisms, and compute their geometric properties. While existing methods to analyze neuron traces focus on macroscopic properties such as branching distribution and path length, the methods here capture the differential properties of neuronal curves in three dimensions.
The methods contained in this dissertation are regularly applied to real data to answer scientific and engineering questions. The tracing environment, ViterBrain, is part of an ongoing project to study the effects of genetic manipulation on axonal projection and branching patterns in developing mice. The experiments in applying diffeomorphisms to neuron traces show that maintaining derivative information is useful if sampling is less than the order of every 10 microns. Our experiments measuring curvature and torsion in neuron branches quantify a notion that many neuroscientists are qualitatively familiar with -- axons are fairly straight when projecting across the brain, but are highly curved in the terminal arbors. Finally, genetic subtypes of serotonergic neurons in the dorsal raphe nucleus have different connectivity patterns, suggesting that more targeted drug therapies for psychiatric disorders are possible.
Opportunities remain to integrate these methods with more advanced image segmentation models, or shape analysis techniques that model curve branching. Nonetheless, this work represents a new perspective on automated neuron tracing and analysis
PROTEIN BINDING TO NUCLEOSOMES IN THE CONTEXT OF HISTONE UBIQUITINATION, METHYLATION, AND PHOSPHORYLATION
No full textIn eukaryotes, a diverse array of site-specific and dynamic post-translational modifications to histone proteins of nucleosomes controls protein binding to nucleosomes. By controlling protein binding to nucleosomes, histone modifications regulate important downstream biological processes like transcription, the DNA damage response, and the cell cycle. Despite progress in studies of the histone modification machinery, many of the complex mechanisms by which histone modifications are deposited, removed, and recognized are still not well understood. This dissertation addresses several unresolved questions. Previous investigations had speculated that ubiquitination of histone H2B lysine 120 (H2BK120ub) excludes proteins from the nucleosome by preventing binding to a negatively-charged surface on the histone core known as the nucleosome acidic patch. I determined a mechanism in which H2BK120ub inhibits protein binding to the nucleosome by occluding the nucleosome acidic patch using cryogenic electron microscopy (cryoEM), electrophoretic mobility shift assays (EMSA), surface plasmon resonance (SPR), and molecular dynamics (MD). In addition, I determined that H2BK120ub may broadly exclude many proteins from the nucleosome using nucleosome affinity proteomics. Phosphorylation of histone H3 threonine 3 (H3T3ph) by Haspin defines the inner centromere of condensed chromosomes ensuring proper progression through mitosis. However, it is not known how Haspin engages the nucleosome to phosphorylate H3T3. I determined the first structure of Haspin bound to nucleosome using cryoEM. This is also the first structure of any histone kinase domain bound to nucleosome. In a unique DNA binding mechanism, Haspin binds to the nucleosome by inserting a positively-charged triple-helix “bundle” into the negatively-charged DNA major groove “pore” at Super-Helical Location (SHL) 5.5. This dissertation helps to decode the complex language of histone modifications by elucidating several key structural mechanisms of fundamental biological processes
Optimization of Electrode Array Design and Stimulus Protocols for a Vestibular Implant
Get PDFBilateral vestibular hypofunction, the loss of vestibular function, can be caused by inner ear injuries, ototoxic drugs, or genetic mutations. Those affected suffer chronic dizziness, fatigue, blurred vision while walking, an increased fall risk, and a decreased quality of life. The current standard of care includes vestibular rehabilitation, which relies on retraining the nervous system to compensate for the deficiency. However, the degree of compensation usually plateaus around 6 months after the onset of symptoms, in part because no other compensatory system can achieve the short latencies of vestibular reflexes. As a result, bilateral vestibular hypofunction often causes lifelong oscillopsia and postural instability.
Implanting electrodes in the semicircular canals and delivering targeted electrical stimulation to the vestibular nerve that encodes head motion has shown promise as a means of partially restoring vestibular sensation. The Johns Hopkins Multichannel Vestibular Implant Early Feasibility Study has unilaterally implanted 14 human participants with vestibular implants. The device has been delivering chronic, motion modulated stimulation for more than 7 years for the subject first enrolled in the trial.
Despite the success observed in that clinical trial, there remains room for improvement to electrode array design and stimulus paradigms. While the current implant has multiple stimulating electrodes and one return electrode, the optimal number and placement of stimulating and return electrodes remains unclear. Currently implemented stimulation paradigms use symmetric and cathodic first pulses, but a more effective stimulus waveform could exist. Additionally, it is unclear whether afferents from the otolith end organs are activated by stimuli vestibular implants typically use to stimulate semicircular canal neurons.
The work described in this dissertation studied those topics in rhesus macaques. First, experiments addressed optimization of the number and location of stimulating and return electrodes. Next, experiments were conducted to determine whether a pulse shape exists that maximizes eye movement speed while minimizing stimulation of nontarget neurons. Finally, the effect of electrical stimulation from a vestibular implant on non-target neurons was assessed via single-unit electrophysiologic recording from individual otolith end organ afferent neurons. This research outlines improvements to the design of a vestibular implant and its stimulus protocols that could be implemented, resulting in a more effective treatment
Neural recycling for programming: exploring the cognitive and neural substrates of a culturally-invented symbol system
No full textProgramming, a culturally invented behavior, possesses transformative potential for modern society, yet its cognitive and neural foundations remain largely unexplored. This dissertation addresses three core questions: What is the neural mechanism “recycled” for programming? How are programming algorithms represented in the brain? What is the cognitive/neural substrates of programming expertise?
Through two functional magnetic resonance imaging (fMRI) experiments involving programming experts and novices, a left-lateralized fronto-parietal network emerges as pivotal for code comprehension in both groups. This network, overlapping with the multiple-demand reasoning network, exhibits responsiveness to algorithms described in plain English even before programming knowledge is acquired, suggesting neural recycling in the lateral fronto-parietal reasoning network.
Multi-variate pattern analyses (MVPA) reveal that neural representations of algorithms are encoded in both the reasoning network and the perisylvian language network, which responds to programming code more weakly but earlier than the reasoning network. The finding suggests that the language network constructs a surface-level representation which is transmitted to the reasoning network for the establishment of a complete and computable representation.
An individual-difference behavioral experiment delves into the correlates of programming learning outcomes, indicating that reasoning, but not language, abilities predict program writing proficiency. Neuroimaging analyses suggest reduced distinctiveness of post-programming education neural representations of algorithms written in plain English. This finding implies that the neural recycling process for programming expertise involves a competition of algorithm-representing neural populations between natural and programming languages.
As an early exploration in the neuroscience of programming, this dissertation provides foundational insights and sets the stage for further investigations into this special case of cultural recycling
RISK ASSESSMENT AND MONITORING OF NON-U.S. BASED RECIPIENTS AND SUB RECIPIENTS: A REVIEW OF BEST PRACTICES
Get PDFThis project aims to prepare small grant-awarding organizations for the growing trend of international research collaborations. Through analysis of best practices of risk assessment in place at research-intensive universities, smaller organizations with less experience administering awards and sub awards to international recipients, and smaller organizations can adapt these procedures to fit their operations with limited resources. Through this, they limit their exposure to the financial and legal risks accompanying international research collaborations, while also fostering cooperation in the future. The analysis and findings will be compared to the single audit reports of the selected organizations to identify strengths and areas for improvement. The aggregate of the most effective controls in place is assembled as reference material and internal control frameworks for small grant-awarding organizations to implement
HEARING THE ALEPH A COLLECTION OF STORIES
Get PDFIn this collection of short stories, Charles Green explores how queerness and art might help us connect with ourselves and others. Drawn from experiences as an arts critic and a gay man, and using elements of speculative fiction, these stories take queer characters to unusual situations and encounters, testing their relationships, their desires, and their secrets
ADVERSE AND POSITIVE CHILDHOOD EXPERIENCES AND GENERAL HEALTH AMONG ASIAN AMERICAN EMERGING ADULTS
Get PDFBackground: Of the limited number of studies reporting the prevalence and impact of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) in Asian Americans, most report a lower prevalence of ACEs among Asian Americans than for other racial/ethnic groups. However, most studies fail to account for the cultural and socioeconomic heterogeneity across diverse Asian ethnic subgroups.
Purpose: This dissertation examined disparities in ACE and PCE exposures in an Asian American sample of emerging adults and described the relationships among ACEs, PCEs, health, and socioeconomic background.
Design and Methods: Using a cross-sectional survey design, Asian American emerging adults (18 - 25 years) self-identified as Asian Indian, Chinese, or Hmong Americans were recruited from November 2021 to November 2022. Participants completed online surveys measuring ACEs (Philadelphia ACEs Survey), PCEs (Benevolent Childhood Experiences Scale), general health (PROMIS Adult Global Health Scale v1.2), and childhood socioeconomic position (CSEP).
Results: In this sample of 814 Asian American emerging adults, 93.4% reported exposure to at least one ACE; 58.9% reported exposure to four or more ACEs. Moreover, 64.7% of participants reported eight or more PCEs. The ACEs and PCEs prevalence differed across the ethnic subgroups with proportionally more Hmong participants reporting four or more ACEs (68.9%) than Asian Indian (52.9%) and Chinese (50.2%) participants. Significantly lower proportion of Hmong participants (56.4%) reported eight to ten PCEs compared to Asian Indian (69.2%) and Chinese (72.3%) participants. CSEP factors accounted for some variations in the ACE and PCE disparities by ethnic subgroups. ACE score was negatively associated with health, and PCE score moderated the negative impact of ACEs on health. Contrary to the hypothesis, higher PCEs did not significantly attenuate the negative association between ACEs and health.
Conclusions: ACEs and PCEs are highly prevalent in this sample of Asian American emerging adults with significant disparities across ethnic subgroups. PCEs moderated the negative association between ACEs and health. Future research should disaggregate data by Asian ethnicity to assess the intersectional impacts of socioeconomic status and race/ethnicity on ACEs and PCEs among Asian Americans. Additional research is needed to further understand the mechanism of the moderating effects of PCEs
tracrRNA regulation of CRISPR-Cas immunity
Get PDFAll immune systems must distinguish self from non-self to carry out immunity against foreign agents while avoiding potentially lethal auto-immunity. Bacterial immune systems are no exception, and must, on a cell-autonomous level, molecularly delineate between foreign and host matter to achieve maximum immunity at minimal costs. The prokaryotic adaptive immune system CRISPR-Cas can obtain, store, and deploy molecular memories of previous bacterial virus (bacteriophage, phage) infection to eliminate future invasions from the same or genetically similar invaders. However, molecular memories can also be acquired from the host genome, leading to the question of how hosts are able to mitigate these costs to support the retention of beneficial CRISPR-Cas systems. One strategy employed to minimize harmful off-target effects of immune systems is the tight regulation of expression or activity of the immune components. However, before our work, nothing was known about how the type II-A CRISPR-Cas system from Streptococcus pyogenes was regulated.
This thesis explores the discovery, characterization, and biological significance of a novel regulator of the bacterial immune system CRISPR-Cas, tracr-L. We find that tracr-L, a non-coding RNA encoded within the CRISPR locus, is able to utilize Cas9 to repress transcription from its own promoter. We provide evidence that while tracr-L is a strong repressor of CRISPR-Cas immunity, tracr-L repression is also a protective mechanism shielding host cells from the negative consequences of Cas overexpression. We explore the evolutionary conservation of tracr-L and speculate on its role in shaping bacterial genome evolution and in facilitating horizontal gene transfer.
We also explore the regulation of tracr-L by phage-encoded anti-CRISPR (Acr) proteins, and how Acr-phage infections can lead to a burst of Cas expression which can serve to increase host survival against phage lysis. Our work demonstrates a novel and direct mechanistic link between phage infection and CRISPR-Cas expression and highlights a strategy hosts can employ to maximize CRISPR-Cas immunity while minimizing auto-immune costs. As such, the tracr-L auto-regulatory circuit represents a weapon in the bacteria-phage arms race that serves as a counter-measure for CRISPR-Cas hosts against the emergence of phage-encoded Acrs