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Eisenstein Series with Class Number Coefficients Constructed from the Weil Representation
Get PDFWe generalize the work found in the paper [KY10] of Kudla and Yang to the case of Hilbert modular forms that come from the Weil representation associated to a 1-dimensional quadratic space. We also provide a computation of the level groups of certain forms produced this way. To achieve our results, we compute closed-form formulas for quadratic Gauss sums over local fields of characteristic 0. This includes the case of both odd and even residue characteristic
CHRONIC TREATMENT WITH SEROTONIN SELECTIVE REUPTAKE INHIBITORS DOES NOT AFFECT REGROWTH OF SEROTONIN AXONS FOLLOWING AMPHETAMINE INJURY IN THE MOUSE FOREBRAIN
Get PDFA current hypothesis to explain the limited recovery following brain and spinal cord trauma derives from the dogma that neurons in the mammalian central nervous system lack the ability to regenerate their axons after injury. Serotonin (5-HT) neurons in the adult brain are a notable exception in that they can slowly regrow their axons following chemical or mechanical lesions. This process of regrowth occurs without intervention over several months and results in anatomical recovery that approximates the pre-injured state. During development, serotonin is a trophic factor, playing a role in both cell survival and axon growth. Additionally, some studies have shown that stroke and traumatic brain injury patients treated after injury with serotonin selective reuptake inhibitors (SSRIs) appeared to have improved recovery of mood, cognition, and even mobility. On the contrary, several other studies have suggested no benefits to treatment with SSRIs following injury beyond the relief of mood.
In this thesis, I tested the hypothesis that serotonin can influence the regrowth of 5-HT axons. Mice received a high dose of para-chloroamphetamine (PCA) to induce widespread retrograde degeneration of 5-HT axons. Then, after a short rest period to avoid any interaction with the acute injury phase, SSRIs were administered daily for 6 or 10 weeks. Using immunohistochemistry in 5-HT transporter promoter driven-GFP BAC transgenic mice, I determined that while PCA led to a rapid initial decrease in total 5-HT axon length in the somatosensory cortex, visual cortex or area CA1 of the hippocampus, treatment with SSRIs did not affect the recovery of axon length. This was true for either of two SSRIs – fluoxetine or sertraline – at each tested dose and duration of administration. As a positive control, daily administration of fluoxetine increased the number of doublecortin positive cells in the dentate gyrus, and daily administration of sertraline increased BDNF expression in the hippocampus.
These results suggest that chronic SSRI treatment does not affect the regrowth of 5-HT axons and argue against SSRIs as a potential therapy following brain injury
Device Characterization for Human Hand and Wrist Motor Control
No full textCurrent therapy tools have limited clinical outcomes for upper-limb recovery due to incomplete models of hand and wrist function that in turn inform device and assessment designs. The purpose of this thesis is to investigate the design of devices and protocols that leverage robotic abilities to collect large datasets for the testing of open hypotheses in neuroscience and functional perception.
Starting with finger mobility, I introduce novel miniature sensors for a tabletop device that records human fingertip forces in 3D task space and in real-time. The goal of the sensors and the larger device is to track and identify abnormal manipulation that may occur in a human hand post-stroke. A rich characterization of the device's sensing capabilities is described, and its implications for dexterity research in identifying finger deficits and treating them through targeted training are discussed.
Then I focus on wrist mobility in the context of teleoperation. Specifically, I summarize the field of teleoperation research, and I focus on findings regarding tool compensation and human tracking. To understand the limits of wrist tracking during teleoperation, I collect performance data from healthy controls attempting to track multiple speed profiles through different dynamics on an existing teleoperator testbed. Our team found that users adjust their wrist control strategy depending on device dynamics, an ability that breaks down as tracking speed gets more difficult. Therefore, there are quantifiable limits to rotational compensation at the wrist.
Lastly for wrist mobility, I discuss how aspects of human proprioception can dissociate depending on context, and I present the concept of a sensory "fingerprints" as a framework for identifying patient-specific patterns of deficit across these aspects. I introduce a new device for testing wrist proprioception and functional ability, and I conduct an assay of multiple psychometric tests and task simulations on healthy controls to find associations between aspects. Our team only found one correlation in rank between passive velocity discrimination and active position matching, and we found that passive and active velocity senses do differ. These findings support the assertion that our device is capable of collecting data needed to generate sensory "fingerprints" for targeted treatment
Exuberant de novo dendritic spine growth in mature neurons
Get PDFDendritic spines are structural correlates of excitatory synapses maintaining stable synaptic communications. However, this strong spine-synapse relationship was mainly characterized in excitatory pyramidal neurons (PyNs), raising a possibility that inferring synaptic density from dendritic spine number may not be universally applied to all neuronal types. Here we found that the ectopic expression of H-Ras increased dendritic protrusion numbers regardless of cortical cell types such as layer 2/3 pyramidal neurons (PyNs), parvalbumin (PV)- and vasoactive intestinal peptide (VIP)-positive interneurons (INs) in the primary motor cortex (M1). The probability of detecting dendritic protrusions, including spines, was positively correlated with the magnitude of H-Ras activity, suggesting elevated local H-Ras activity is involved in the process of dendritic spine formation. H-Ras overexpression caused a high spine turnover rate via adding more protrusions rather than eliminating them. Two-photon photolysis of glutamate triggered de novo dendritic spine formation in mature neurons, suggesting H-Ras-induced spine formation is not restricted to early development. In PyNs and PV-INs, but not VIP-INs, we observed a shift in average spine neck length towards longer filopodia-like phenotypes. The portion of dendritic protrusions lacking key excitatory synaptic proteins was significantly increased in H-Ras transfected neurons, suggesting that these increased protrusions, including spines, may not be functional. Consistent with this, high protrusion density caused by H-Ras did not result in a change in the frequency or the amplitude of miniature excitatory postsynaptic currents (mEPSCs). Thus, our results propose that dendritic protrusions, including spines, possess more multifaceted functions beyond the morphological proxy of the excitatory synapse
RETHINKING PRACTICE: A GUIDE TO DESIGNING VISITOR-CENTERED EXPERIENCES IN ART EXHIBITIONS
Get PDFArt exhibitions are informal learning environments that offer visitors wide-ranging possibilities for meaningful engagement with the arts. However, art exhibitions have been associated with social and cultural exclusion as specialized language in exhibition texts and labels may pose barriers to visitors unfamiliar with the art world. Through a multi-method approach, an empirical study was conducted to understand visitors' perceptions of their experience at an art exhibition in Guatemala City and the role of museum texts and labels. Findings revealed participants (n = 13) described their experience as connected to reflection, aesthetic appreciation, and peacefulness. The art exhibition had two types of labels. Participants perceived exhibition texts and labels both as too intellectual and oversimplified. Informed by an exploration of the literature focused on designing art exhibitions for specific purposes, this dissertation developed a guide for practice containing a framework for critical reflection, research-informed practice, and collaborative inquiry. The guide's purpose is to support practitioners by offering a tool to reflect on their work and consider the visitor as central to the process of designing an art exhibition
Practical Matters: Rational Human Agents in the Making
No full textMetaethical constitutivists seek to ground the rational authority of reasons for actions—what makes certain actions right to do on pain of irrationality—in constitutive features of our form of agency. According to constitutivists, what makes something right to do is ultimately grounded in norms to which rational human agents are subject simply in virtue of the kind of agents they are. The dissertation develops a novel constitutivist account of the kind of agency exercised by rational human beings. On this account, a constitutive feature of our form of agency is the fact that our relation to our ends is mediated by our capacity to generate the means by which they can be taken up and pursued. This applies, in the first instance, to the material conditions in which these ends are pursued, and in the second, to the concepts with which represent these ends our relation to them. In both cases, the relations in which human beings stand to their ends are mediated by what they themselves make possible by developing the tools with which to think and act. The dissertation argues that the mediating role that our productive capacities play in our capacity to pursue our ends is a defining feature of our being rational animals, but one that has been mostly neglected by other constitutivists. The dissertation develops this claim on both a metanormative and a normative level: on the metanormative side, it aims to vindicate the production of the means for the pursuit of our ends as the constitutive principle of rational human agency; on the normative level, it aims to show that this conception of agency can provide a substantive explanation for what makes particular norms of practical rationality the right ones. In developing each of these claims, the dissertation shows how constitutivism can be defended against its more serious objections
Image-Guided High-Dexterity Robotic Systems for Minimally Invasive Orthopaedic Surgery
No full textExpanding the reach and utility of minimally invasive procedures in orthopaedic surgery to improve patient outcomes presents several challenges. These procedures require an accurate understanding of the location of surgical tools relative to critical patient anatomy, often in the absence of direct line of sight or any single high-fidelity data stream. Minimizing procedure invasiveness by adding dexterity and maneuverability to tools can allow access to harder-to-reach surgical sites with less impact to tissue along the way and navigation along more complex trajectories. These tools still must be capable of tissue manipulation or removal at the anatomy of interest, but the added complexity increases the difficulty of accurate localization and navigation. Together, these challenges motivate the development of image-guided high-dexterity robotic systems that can be used to perform minimally invasive procedures in orthopaedic surgery.
Such a robotic system would serve as an enabling tool to assist surgeons during minimally invasive procedures and may autonomously perform a set of tasks. Several critical components are needed including dexterous tooling, sensing technologies, control strategies, robotic manipulation, user interfaces, and surgical planning tools. No single component alone is sufficient to solve these complex surgical challenges and a systems-centric consideration is critical to development. This dissertation presents the development and integration of several system realizations, building in complexity towards an image-guided high-dexterity robotic system. We present a system framework and control architecture, consider strategies for guidance using X-ray imaging and additional sensors, incorporate dexterous tooling, and explore strategies for expanding the design and integration of these components. Applications in minimally invasive spine and hip surgery are presented to demonstrate the utility of these systems in clinical procedures. Further, a system-level surgical simulation platform is presented to enable the development and testing of these systems by increasing the rate, feasibility, and safety of new strategy experimentation. This platform contributes to the growing movement to incorporate 'digital twins' in computer-aided interventions, and several contributions to the state-of-the-art in orthopaedic surgical simulation are presented.
We believe these contributions can serve as a foundation for the development of future image-guided high-dexterity robotic systems for minimally invasive orthopaedic surgery, both to enable more rapid and effective research systems, as well as to enable future clinical systems to have a broader impact on patient care
ASSESSING THE EFFECTIVENESS OF PROFESSIONAL DEVELOPMENT TO CLOSE THE ACHIEVEMENT GAP BETWEEN STUDENTS WITH DISABILITIES AND THEIR NON-DISABLED PEERS IN INCLUSION CLASSROOM SETTINGS
Get PDFThe Individuals with Disabilities Education Act (IDEA) and the No Child Left Behind Act
(NCLB) emphasize improved academic outcomes for students with disabilities. Additionally,
IDEA ensures that public and private school students have the right to be educated with their
non-disabled peers in the least restrictive environment. Students with disabilities (SWDs) spend
at least 80% of their time in the general education setting. However only 8% of SWDs in
Washington, DC perform on grade level, compared to 50% of students without disabilities
performing on grade level. Using focus groups and surveys, teachers in Washington, DC were
able to share their experiences, perspectives, and views regarding teaching SWDs in their
inclusion classrooms. The results of this qualitative study showed that teachers desire more
professional development around special education law, pedagogy, and IEPs to feel more
confident using inclusion pedagogy to support teaching SWDs
IDENTIFYING PROTEIN-PROTEIN INTERACTIONS VIA CROSSLINKING MASS SPECTROMETRY: CHARACTERIZING DYNAMIC ENSEMBLES, DISORDERED REGIONS, AND PROTEOME-WIDE INTERACTION NETWORKS
Get PDFIn the past decade, crosslinking mass spectrometry (XL-MS) has emerged
as a transformative tool in structural biology investigations. Its primary strength
lies in providing structural information through the identification of protein-protein
interactions as 3-D information and distance constraints, elucidating the modes
of formation in complex ensembles, or identifying the interactions of intrinsically
disordered species. These aspects, often elusive to other analytical techniques,
highlight the unique and impactful role of XL-MS in advancing our understanding
of protein structures in diverse biological contexts.
This dissertation describes several photo-crosslinking tools and their
applications in chemical and structural biology. This work underscores the
significance of investigating the “molecular sociology” of proteins to comprehend
both the molecular structure and dynamics of complexes, along with their
underlying biological mechanisms that sustain life
ETIOLOGY AND PREVENTION OF LATE-LIFE FRAILTY: A PROTEOMIC APPROACH
No full textBackground: Understanding the etiology and effectiveness of intervention strategies are two important research areas to help reduce frailty, a syndrome of reduced reserve and increased vulnerability that predicts adverse health outcomes in older adults. Proteomic studies are emerging to explore novel biological processes of frailty and to understand the benefits of physical activity (PA), a promising intervention strategy for frailty. However, knowledge gaps include protein signatures of prefrailty and incident frailty, mid-life protein signatures of frailty, and the effect of long-term physical activity in daily life on frailty-associated proteins.
Methods: First, we used multinomial regression and logistic regression models to identify late-life proteins cross-sectionally associated with prefrailty and/or frailty and with incident frailty by the end of a 6-year follow-up, respectively. Next, we used multinomial regression models to identify mid-life proteins associated with late-life prefrailty and frailty. The biological functions of the discovered proteins were annotated using pathway and upstream regulator analyses. Finally, we leveraged a target trial emulation design and two methods for time-varying exposure to estimate the effects of achieving and maintaining the recommended ≥150 minutes/week of moderate-to-vigorous physical activity (MVPA) in mid-life on the 45 top mid-life frailty-associated proteins.
Results: In late-life, over 300 proteins were cross-sectionally associated with both prefrailty and frailty, 15 of which were also associated with incident frailty. In mid-life, 12 and 221 proteins were associated with late-life prefrailty and frailty, respectively. Several proteins were associated with frailty status in both life stages, but many other proteins were significant for only one life stage. Inflammation, metabolism, angiogenesis, and extracellular matrix were implicated in both life stages. Achieving and maintaining ≥150 minutes/week of MVPA in mid-life had beneficial effects on multiple mid-life frailty-associated proteins involved in nervous system and inflammation.
Conclusion: Proteins involved in frailty development may differ at different life stages and mid-life physical activity may have benefits on the pathophysiology of frailty. Discovered proteins from this dissertation can be targeted for future investigation into potential causal roles of the proteins and targets for interventions. Findings on mid-life PA suggest that long-term adherence to the recommended PA guideline should be encouraged among middle-aged adults