The Search for and Formation of Synapses on Zebrafish Motoneurons Across Natural Periods of Activity and Quiescence

DiPietro, Joseph Victor, Jr ProQuest Dissertations & Theses Cornell University 2017 해외박사(DDOD)

The work presented in this dissertation is an in-depth analysis of how a single neuron, the primary motoneuron of zebrafish, searches for and forms synapses across the circadian periods of activity and quiescence that occur from day to night. Dendrites repeatedly extend and retract filopodia in a search for synapses, the formation of which stabilizes the process, leading to growth of the arbor. I first focused my attention on zebrafish primary neurons during the day to explore, for the first time, the search process from the level of individual filopodial dynamics to the distribution of dynamics across an entire dendritic arbor. We found the magnitude of searching at individual locations varied tremendously across locations, with filopodia extending and retracting as much as 3 microns and averaging about 12 dynamics events per filopodium in a given 30-minute period. An analysis of the temporal sequence of these dynamic events showed the pattern of dynamics at individual locations also varied tremendously. Only retractions showed a consistent trend, tending to stabilize for some time and rarely being followed by an extension. This shows that dendrites are not just simply extending and stabilizing filopodia. Instead, filopodia at each individual location are engaging in highly dynamic periods of searching, with most extensions retracting within 5 minutes. Only about 4% of extensions survive for an hour or more, possibly representing the formation of synapses. We further find that these dynamic locations are equally distributed across the dendrite arbor independent of their individual dynamics and only the furthest extents of dendrite had higher than average numbers of motile locations, suggesting the search is largely unbiased except for those furthest regions. A comparison of how the search differs between day and night shows surprisingly, that the magnitude of this searching increases at night, a quiescent time, when motoneuron are much less active. While the extensions at night are less likely to stabilize, this increase in searching may partly account for these cells still forming synapses at a similar rate as during the day, with only the rate of synapse removal changing, increasing significantly at night. These results demonstrate that during times of behavioral and activity quiescence, neurons continue to search for and form synapses at the expense of losing others, providing potential insight into the role these quiescent states may play in network development and neuronal plasticity.

Common Properties of Social Accounts in Meetings that Promote Forgiveness and Conflict Resolution

Mroz, Joseph E ProQuest Dissertations & Theses University of Nebr 2019 해외박사(DDOD)

After doing something wrong, people frequently provide an account, or explanation, for their behavior to others. Although social accounts have been studied for decades, emerging findings that are in conflict with one another regarding the “best” type of social account continue to proliferate. One reason for continued lack of clarity may be that social accounts operationalized theoretically and within laboratory settings do not align with how accounts are used in everyday social interactions. In this dissertation, I conducted two studies with aims of (a) classifying and describing whether actual accounts align with or diverge from those established theoretically in the literature and (b) assessing whether using a combination of features from multiple types of accounts promotes decreased negative responses when compared to the unadulterated form of each type of explanation. These studies used the context of arriving late to a workplace meeting as the social transgression. Results suggested that an expression of remorse, an aspect of apologies, is the most common feature of accounts in response to arriving late to a meeting. In addition, only components of apologies exhibited any effect of post-transgression reactions. Implications of these findings and future directions are discussed.

Non-Tonal Pitch Hierarchies and Dramatic Narratives in Oliver Knussen's Variations, Op. 24

Prestamo, Joseph ProQuest Dissertations & Theses City University of 2022 해외박사(DDOD)

Musical analysts have often commented on the lingering echoes of tonality present within the otherwise non-centered (and remarkably complex) harmonic world of Oliver Knussen’s music. Using his piece Variations, Op. 24 as a model, this project hypothesizes that the compositional techniques Knussen employs serve to create non-tonal pitch hierarchies. Although Knussen does not use functional tonal harmony in this piece, he finds a variety of ways to elevate the pitch A to a place of prominence, both on the musical surface and in the background structural operations. These techniques naturally result in pitch spaces that are rich with tonal and modal implications, but Knussen approaches these spaces using entirely non-tonal frameworks. This project also examines Knussen’s impeccable sense of timing and drama, and attempts to identify the compositional elements that contribute to the pacing and form of this composition. I uncover intricate layers of musical material on separate but interconnected trajectories, and formal sections that are both discrete and dovetailed, all contributing to what Knussen calls the “big shape of the piece.”.

Exacting encounters: Objectivity and literality in early Victorian realism

Bishop, Benjamin Joseph University of California, Irvine 2010 해외박사(DDOD)

"Exacting Encounters" investigates a disruption of the effort in realism to organize the world into already secured categories by the emergence of objectivity, which obstructs the capacity of early Victorians to correlate the world to themselves. Rather than understand this rupture as the cause of some irreparable crises of the subject brought on by an "end" of representation, my dissertation argues that the encounter with irregularity fixes the attention of early realists who respond to the particularity of their worlds with an experimental realism that employs a precise rhetorical and graphical manipulation of letter and line. Chapter one begins by showing how realism is initially outsourced to the British Empire where Edwards Lane exploits Egyptian resources with an exhaustive account of its terrain, imbuing it with an "exoticism" that sustains an interest in the prosaic work of description, which, in turn, unsettles Lane's ability to narrate himself as a member of the world he explores. Chapter two shows how Dickens's surrogate narrator, Esther, faces a different kind of narrative disruption in Bleak House, where unending metonymic displacement produces a world that makes everything a part of it. She patiently handles this by pushing the trope it to its most extreme limits where letters give way to literal blanks, uncovering a way out of the novel's constrictive cosmos. These problems of disruption extend beyond narratological methods of organization and chapter three shows how William Whewell theorizes this early realist problem with an unusual commitment to an ontological inconsistency between necessary form and the existence of empirical reality that is at first shored up with what we calls a "permanent line." He eventually literalizes this metaphor with a one dimensional line that no longer names the division but literally inscribes it. Chapter four investigates how John Ruskin's Modern Painters conditions its aesthetic principles on the subject's capacity to achieve a proportion between what he experiences and what nature exhibits. This causes Ruskin to place an excessive check to metaphor and steady himself through the textual limitations of geometry where his own place is determined by a single point on the perspective plane.

Characterizing Putative Driver Events in Cancer: Fast-Cycling with RAC1 and Oncogenic Stabilization of a Dominant-Negative CBL Mutation

Davis, Matthew Joseph Yale University 2015 해외박사(DDOD)

It is well understood that cancer is a disease of the genome. Large second-generation genomic cataloguing efforts have proven useful in identifying a constellation of cancer associated mutations in numerous genes whose pattern have helped stratify patient population treatment, aid in diagnoses and understand basic tumor biology. However, as genomic instability is one of the 'hallmarks of cancer' questions of cause and effect are understandably important. Accordingly, cancer associated genes are broadly designated as 'drivers,' genes that contribute to the cancers progression, and 'passengers,' genes that are not vital to cancers progression. Thus, it is important prioritize putative cancer 'driver' genes for specific biochemical function. Cancer subtypes including melanoma and lung adenocarcinoma (LUAD) reveal the importance of identifying and more importantly understanding the 'driver' events underlying their respective progression. Specifically, gain-offunction 'driver' genes including BRAF and EGFR in melanoma and LUAD respectively have been targeted pharmacologically leading to great clinical impact. Consequently, these successes have fueled fervent efforts to discover and understand other potentially tractable 'driver' events in these devastating diseases. Therefore I have focused my investigations on the identification and functional validation of putative 'driver' events, specifically a recurrent point mutation in RAC1 identified in melanoma and a recurrent splice-variant in CBL identified in LUAD. RAC1 is a small, Ras-related GTPase that was recently reported to harbor a recurrent UV-induced signature mutation in melanoma, resulting in substitution of P29 to serine (RAC1P29S), ranking this the third most frequently occurring gain-offunction mutation in melanoma. Although the Ras-family GTPases are mutated in about 30% of all cancers, mutations in the Rho family GTPases have rarely been observed. In this study, we demonstrate that unlike oncogenic Ras proteins, which are primarily activated by mutations that eliminate GTPase activity, the activated melanoma RAC1P29S protein maintains intrinsic GTP hydrolysis and is spontaneously activated by substantially increased inherent GDP/GTP nucleotide exchange. Determination and comparison of crystal structures for activated RAC1 GTPases suggest that RAC1F28L--a known spontaneously activated RAC1 mutant--and RAC1P29S are self-activated in distinct fashions. Moreover, the mechanism of RAC1P29S and RAC1F28L activation differs from the common oncogenic mutations found in Ras-like GTPases that abrogate GTP hydrolysis. The melanoma RAC1P29S gain-of-function point mutation therefore represents a previously undescribed class of cancer-related GTPase activity. CBL is a multidomain adaptor protein endowed with E3 ubiquitin ligase activity and prominently involved in the negative regulation of numerous protein tyrosine kinases (PTKs) including receptor tyrosine kinases (RTKs) like EGFR and MET. Through a collaborative whole exome-sequencing (WES) project of LUAD samples it was determined that CBL accumulates somatic mutations. Furthermore, recurrent mutations were found in canonical splice sites surrounding exon 8 of CBL (both upstream and downstream), which are known to cause exon-skipping leading to the expression of a protein that lacks the 44 residues encompassing exon 8 (CBLDelta8). Exon 8 encodes a portion of the linker region and RING domain of CBL, which are responsible for E3 ligase activity. Thus it was hypothesized that CBLDelta8 would not be able to ubiquitinate protein substrates and perhaps allow for potentiation of certain RTK signaling. Furthermore, as the EGFR signaling cascade is of significant interest in LUAD we suggest that patients harboring certain mutant CBL proteins may benefit from EGFR targeted inhibition. In live cancer-derived cells I show that CBLDelta8 acts in a dominant-negative fashion where it is unable to properly ubiquintate EGFR allowing for abrogated degradation and prolonged activation post ligand stimulation. However, in untransformed cell lines including CBL -/- mouse embryonic fibroblasts (MEFs) it was shown that CBLDelta8 protein stability is compromised via constitutive proteosomal degradation not allowing for the mutant to exert its dominant-negative function on EGFR signaling. I suggest that the CBLDelta8 mutant requires the oncogenic cell state in order to act as an oncogene while in the normal untransformed cellular state the protein will act as a null allele. Overall I have utilized a variety in vitro biochemical and cellular assays to functionally characterize potential novel `driver' events in two major cancer subtypes. Both RAC1 P29S and CBLDelta8 are novel in function and provide interesting insight into the broad array of mutation and their functionality in cancer.

Exploring the influence of an American Latina/o intellectual formation in flux: An analysis of the multiform capital and protocultural agency accumulated by the avowed Raza Mezclada vanguard

Villescas, Joseph Paul-Anthony The University of Texas at Austin 2006 해외박사(DDOD)

This dissertation explores how the emergence of a critical consciousness regarding the advantageous racial mutability and hybridity of social agents positioned throughout an intellectual formation of U.S. Latina/os may be entropically destabilizing their social collective's longstanding beliefs about race that ultimately undergird the microcosmic and macrocosmic systems of power. Although the racialization of Latina/os was not a focus of Bourdieu's inquiries, recent Latina/o-oriented investigations, particularly Rojas' 2003 investigation of Latinas' representations and self-perceptions, occurring throughout Multicultural Media Studies, an emergent area of inquiry where Cultural Studies, Media Studies, and Reflexive Sociology collide, have utilized components of his theoretical framework to interpret phenomena occurring within subsectors of the multidimensional Latina/o social collective. In this Multicultural Media Studies investigation, Bourdieu's theories are not only utilized to explore how this recent generation of the educated vanguard of Latina/o agents born after 1975 resist and reinforce the 'fields of race' and the 'field of power' through their efficient amassment as well as conversion of 'multiform' capital in dominant modes, but are also applied to a discussion of their social trajectories when configured as a 'quasiracial' White Latina/o, 'monoracial' Latina/o, and 'polyracial' Latina/o (i.e., what the author identifies as Raza Mezclada) intelligentsia. Through statistical analyses of their responses to a calibrated on-line survey that was launched throughout Texas during the fall of 2005, this investigation of an intellectual formation comprised of Latina/o undergraduate (i.e., bachelor of arts/science) and graduate (i.e., master of arts/science, professional, and doctoral) degree seekers attempts to determine how these social agents perceive their individual and collective capacities to preserve, alter, or dissolve the current system of racial classification (i.e., social stratification through racial differentiation) through the recovery of agency derived from their racial mutability and/or hybridity. Although the author and multiple participants perceive the current era to be one of increasing resistance to the conventional American logics, schemes, and representations of race, and thus to the race-based 'habitus' that preserve the field of power, the conclusions of this investigation suggest that multiple sectors of this intellectual vanguard possess distinct social advantages through their embracement of their racial mutability and hybridity.

Group processes and ecosystem-based management: An in-depth qualitative case study of a multi-stakeholder watershed management group

Bonnell, Joseph Ellis The Ohio State University 2001 해외박사(DDOD)

Ecosystem-based management (ESBM) is an emerging approach to managing natural resources that involves multiple stakeholders finding collaborative solutions to complex resource management issues from a whole-system perspective. For several years, researchers have been asking what makes some ecosystem-based management efforts more successful than others. To date, investigations have focused on describing how ESBM differs from traditional resource management approaches, describing outcomes (e.g., participant satisfaction, decision quality) of ESBM processes, and identifying the social structures that promote or inhibit ESBM efforts. Despite all the recent attention to ESBM groups, we still have limited understanding of how multi-stakeholder groups organize and function over time as they attempt to implement an ESBM approach. The purpose of this investigation was to compare the practice of ESBM with the concept of ESBM as described in the literature through an in-depth case study describing and exploring the actions and interactions of the Little Miami River Partnership (LMRP) Board of Directors as they implemented an ecosystem-based approach to managing the Little Miami River watershed. The primary methods of data collection were in-depth interviews with Board of Directors (herafter referred to as Board) members and observations of Board meetings. Data were analyzed in relation to ESBM concepts. Findings from this study indicate a high correspondence of ESBM practice and theory. The LMRP Board of Directors were concerned with broad-based stakeholder involvement in collaborative resource management planning from a whole system perspective. Board members had difficulty defining the group's purpose and developing goals for collaboration and coordination. The group was characterized by flexible roles and ambiguity around the issue of representation. Findings from the study suggest the need for more research integrating group communication and ESBM theory.

Design and implementation of an FPGA-based piecewise affine Kalman Filter for Cyber-Physical Systems

Mills, Aaron Joseph Iowa State University 2016 해외박사(DDOD)

The Kalman Filter is a robust tool often employed as a process observer in Cyber-Physical Systems. However, in the general case the high computational cost, especially for large plant models or fast sample rates, makes it an impractical choice for typical low-power microcontrollers. Furthermore, although industry trends towards tighter integration are supported by powerful high-end System-on-Chip software processors, this consolidation complicates the ability for a controls engineer to verify correct behavior of the system under all conditions, which is important in safety-critical systems and systems demanding a high degree of reliability. Dedicated Field-Programmable Gate Array (FPGA) hardware can provide application speedup, design partitioning in mixed-criticality systems, and fully deterministic timing, which helps ensure a control system behaves identically to offline simulations. This dissertation presents a new design methodology which can be leveraged to yield such benefits. Although this dissertation focuses on the Kalman Filter, the method is general enough to be extended to other compute-intensive algorithms which rely on state-space modeling. For the first part, the core idea is that decomposing the Kalman Filter algorithm from a strictly linear perspective leads to a more generalized architecture with increased performance compared to approaches which focus on nonlinear filters (e.g. Extended Kalman Filter). Our contribution is a broadly-applicable hardware-software architecture for a linear Kalman Filter whose operating domain is extended through online model swapping. A supporting application-agnostic performance and resource analysis is provided. For the second part, we identify limitations of the mixed hardware-software method and demonstrate how to leverage hardware-based region identification in order to develop a strictly hardware-only Kalman Filter which maintains a large operating domain. The resulting hardware processor is partitioned from low criticality software tasks running on a supervising software processor and enables vastly simplified timing validation.

Boundary-Layer Transition on a Slender Cone in Hypervelocity Flow with Real Gas Effects

Jewell, Joseph Stephen California Institute of Technology 2014 해외박사(DDOD)

The laminar to turbulent transition process in boundary layer flows in thermochemical nonequilibrium at high enthalpy is measured and characterized. Experiments are performed in the T5 Hypervelocity Reflected Shock Tunnel at Caltech, using a 1 m length 5-degree half angle axisymmetric cone instrumented with 80 fast-response annular thermocouples, complemented by boundary layer stability computations using the STABL software suite. A new mixing tank is added to the shock tube fill apparatus for premixed freestream gas experiments, and a new cleaning procedure results in more consistent transition measurements. Transition location is nondimensionalized using a scaling with the boundary layer thickness, which is correlated with the acoustic properties of the boundary layer, and compared with parabolized stability equation (PSE) analysis. In these nondimensionalized terms, transition delay with increasing CO2 concentration is observed: tests in 100% and 50% CO2, by mass, transition up to 25% and 15% later, respectively, than air experiments. These results are consistent with previous work indicating that CO2 molecules at elevated temperatures absorb acoustic instabilities in the MHz range, which is the expected frequency of the Mack second-mode instability at these conditions, and also consistent with predictions from PSE analysis. A strong unit Reynolds number effect is observed, which is believed to arise from tunnel noise. NTr for air from 5.4 to 13.2 is computed, substantially higher than previously reported for noisy facilities. Time- and spatially-resolved heat transfer traces are used to track the propagation of turbulent spots, and convection rates at 90%, 76%, and 63% of the boundary layer edge velocity, respectively, are observed for the leading edge, centroid, and trailing edge of the spots. A model constructed with these spot propagation parameters is used to infer spot generation rates from measured transition onset to completion distance. Finally, a novel method to control transition location with boundary layer gas injection is investigated. An appropriate porous-metal injector section for the cone is designed and fabricated, and the efficacy of injected CO2 for delaying transition is gauged at various mass flow rates, and compared with both no injection and chemically inert argon injection cases. While CO2 injection seems to delay transition, and argon injection seems to promote it, the experimental results are inconclusive and matching computations do not predict a reduction in N factor from any CO2 injection condition computed.

Physical Optics Based Computational Imaging Systems

Olivas, Stephen Joseph University of California, San Diego 2015 해외박사(DDOD)

There is an ongoing demand on behalf of the consumer, medical and military industries to make lighter weight, higher resolution, wider field-of-view and extended depth-of-focus cameras. This leads to design trade-offs between performance and cost, be it size, weight, power, or expense. This has brought attention to finding new ways to extend the design space while adhering to cost constraints. Extending the functionality of an imager in order to achieve extraordinary performance is a common theme of computational imaging, a field of study which uses additional hardware along with tailored algorithms to formulate and solve inverse problems in imaging. This dissertation details four specific systems within this emerging field: a Fiber Bundle Relayed Imaging System, an Extended Depth-of-Focus Imaging System, a Platform Motion Blur Image Restoration System, and a Compressive Imaging System. The Fiber Bundle Relayed Imaging System is part of a larger project, where the work presented in this thesis was to use image processing techniques to mitigate problems inherent to fiber bundle image relay and then, form high-resolution wide field-of-view panoramas captured from multiple sensors within a custom state-of-the-art imager. The Extended Depth-of-Focus System goals were to characterize the angular and depth dependence of the PSF of a focal swept imager in order to increase the acceptably focused imaged scene depth. The goal of the Platform Motion Blur Image Restoration System was to build a system that can capture a high signal-to-noise ratio (SNR), long-exposure image which is inherently blurred while at the same time capturing motion data using additional optical sensors in order to deblur the degraded images. Lastly, the objective of the Compressive Imager was to design and build a system functionally similar to the Single Pixel Camera and use it to test new sampling methods for image generation and to characterize it against a traditional camera. These computational imaging systems share a common theme in that they seek to accomplish camera designs that meet more demanding system requirements through the use of additional measurements made possible by hardware modifications, while relying on modeling and computational methods in order to provide valuable scene information.