Conical Shock Wave Turbulent Boundary Layer Interactions in a Circular Test Section at Mach 2.5

Sasson, Jonathan Case Western Reserve University ProQuest Dissertat 2022 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

A series of experiments were performed at Mach 2.5 in a circular test section in an effort to characterize an impinging/reflected shock wave turbulent boundary layer interaction generated by a cone, and provide benchmark quality datasets for CFD validation without the pitfalls inherent in rectangular configurations. Three different cone angles were used in the experiments to study unseparated and separated interaction. Three dimensional interactions were also created by offsetting the cone from the test section centerline. The experiments included surface flow visualization, static wall and pitot pressure measurements, and normal hot-wire measurements. The hot-wire measurements were used to calculate mean mass fluxes and total temperatures, turbulence intensities, and a mass flux signal. A series of calculations were also performed, ranging from simple inviscid one-dimensional numerical methods to more complex three-dimensional RANS CFD were performed in an effort to show the gaps between these techniques and experimental data. Surface flow visualization and static pressure showed that the spatial extent of the shock wave turbulent boundary layer interaction increased with increasing cone angle. The maximum static pressure was found to also increase with increasing cone angle, and to vary with circumferential angle. In the asymmetric configurations, the maximum pressure was found when the shock generator was closest to the test section centerline. The probability density functions near the wall in the interaction region were found to be bimodal for the separated cases. Evidence of reflected shock unsteadiness was also seen as bimodal distributions in the probability density functions. The power spectral densities showed increased low frequency contributions in the separated regions, with a peak frequency one order of magnitude lower than the incoming intermittent boundary layer turbulence frequency. Downstream of the interaction, the reflected shock wave continued to influence the boundary, with peak frequencies near the edge of the boundary layer corresponding to the zero-crossing frequency of the reflected shockwave in the interaction region. For the asymmetric interactions, normal hot-wire measurements were only taken at locations where the cone was closest to and furthest away from the wall. From streamwise measurements, no discernable difference was observed between the symmetric and asymmetric interactions.

Integrated Computational Drug Discovery Approaches for Neuropsychiatric Disorders

Zhou, Mengshi Case Western Reserve University ProQuest Dissertat 2020 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Neuropsychiatric disorders (NPDs) such as Alzheimer's disease (AD) lead to enormous societal burdens. Current treatments of NPDs have limitations, and the drug development process is at a standstill. In this dissertation, we proposed integrated computational approaches to facilitate NPDs drug discovery. First, we developed data-driven system approaches to identify FDA-approved drugs that may target NPDs-related genes. We developed a novel network-based model for drug-target interaction (DTI) prediction by preserving context-specific drug-side effect relationships. Our new network model improved DTI prediction comparing to the traditional similarity-based network model. Furthermore, we extended our model by modeling 855,904 phenotypic and genetic relationships among 24,600 biomedical entities and constructed a DTI prediction system (TargetPredict). Next, TargetPredict was used to identify the FDA-approved drugs that may target AD-associated genes. The AD drugs identified by TargetPredict were associated with lower risks of AD and dementia in electronic health record (EHR) data of 17 million patients over 65 years old. Second, we developed a phenome-driven computational drug repositioning approach to identify NPDs treatments without known NPDs-related genes. Our approach hypothesized that similar drugs treat the same diseases. We applied the approach to Drug addiction (DA), assuming that new treatments share similar phenotypes and common targets with drugs that cause or treat DA. Our method could prioritize FDA-approved and not-yet-approved DA drugs. The top-ranked DA drug candidates may play a beneficial role regarding remission from dependence in 326,340 opioid-dependent patients’ EHR data. The pathway-enrichment analysis supported this clinical observation.Third, we performed an EHRs-based retrospective case-control study of 56 million adults (age ≥ 18 years) to study the relationships between tumor necrosis factor (TNF)-mediated systemic inflammation and AD, and the potential of using anti-TNF drugs as AD treatments. We found the co-morbid inflammatory disease involving TNF was associated with an increased risk of AD, and this could be mitigated from the treatment of a TNF blocking agent. In conclusion, our studies, including computational drug target prediction, drug repositioning, and retrospective clinical corroboration, can rapidly identify anti-NPDs drug candidates. Those drug candidates will allow biomedical researchers to conduct hypothesis-driven functional studies in experimental models for NPDs.

An Exploration of Musical Habits of Alumni from “The Lakewood Project” and How They Musick after High School

Hankins, Elizabeth Aylmer Case Western Reserve University ProQuest Dissertat 2017 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

An Exploration of Musical Habits of Alumni from “The Lakewood Project” and How They Musick After High SchoolBy ELIZABETH AYLMER HANKINSThe purpose of this multiple case study was to explore the musical habits of alumni from The Lakewood Project (TLP), a high school rock orchestra whose alumni tend to participate in music making experiences after high school at a high rate. Two lenses were used to explore this phenomenon. First, Christopher Small (1999) defined musicking as a person contributing, in any capacity, to a musical performance or in any activity that adds to the human encounter of music. Second, Situated Learning Theory, a theory derived from the apprenticeship model, stating that students are more inclined to learn when actively participating in their learning. Both components have been the bedrock of TLP environment. Thus, the research questions in this study included (1) the ways in which TLP alumni were motivated and enabled to musick after high school, (2) how TLP learning environment emulated their current musicking environment, (3) what aspects of formal music learning and informal music learning have they continued to use, and (4) what skills or knowledge were missing from their TLP experience. This multiple case study was based on ethnographic data collection techniques and included five TLP alumni. Data were collected through observations, interviews, and participant artifacts. Codes and themes were assigned following data analysis. Themes included musical motivation, voluntary risk-taking, the musical zone, camaraderie, and democratic collaboration. Within-case and cross-case analysis produced overarching themes, including a well-trained ear; arranging, composing, and improvising; knowledge of technology; and the ability to develop and implement performances. Unexpected findings included participants’ motivation to give back to younger musicians and their comfort with failure. Embracing failure as an opportunity to achieve greater success. Because one mission of music education has been to enable students to continue musicking after high school, several compelling implications were drawn from this study. Exposing students to formal and informal learning skills can empower them to make music in all settings and genres. Furthermore, teaching students to self-diagnosis musical problems; communicate musical concerns to others in a constructive way; and create scenarios that build confidence and empower them to take chances may lead to productive jobs and performances.

Understanding the Molecular Mechanism of TRP Channel Activation/Inhibition by Structural Analysis

Samanta, Amrita Case Western Reserve University ProQuest Dissertat 2018 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Transient Receptor Potential (TRP) superfamily of ion channels are evolutionarily conserved integral membrane proteins. The 28 members of the mammalian TRP superfamily are cation permeable channels which are grouped into six subfamilies based on their sequence homology. This superfamily of ion channels is involved in a vast array of physiological and pathophysiological processes including cancer, neuropathic pain, cardiovascular disease, inflammation, diabetes and polycystic kidney disease. Therefore, the study of these channels is imperative to our better understanding of subcellular biochemistry. The latter half of the 20th century marked the discovery of TRP channels and a lot is known about their physiological characteristics and functions. But until the last couple of years, not much was known about their structure and molecular mechanisms underlying their biophysical and physiological properties. Here I utilized our ability to heterologously express and purify full length, stable and functional mammalian TRP channels to gain insight into the molecular mechanism of gating of two of the TRP channels: TRPV2 and TRPA1. Using cannabidiol (CBD), an activator of TRPV2 channel, we tested the hypothesis that the pore turret region of the channel is important for opening of its ion conduction pore and could also capture the open state structure of TRPV2 using cryo electron microscopy (cryo-EM) revealing the gating mechanism of this channel during activation. In case of TRPA1, it was known that certain cysteine residues are critical for channel activation with electrophilic ligands, however the mechanism of channel gating was unknown. Moreover, not much was known about effect of non-electrophilic modulators on this channel. In second part of this study I illustrated the regions of TRPA1 ion channel that undergoes ligand induced conformational changes using limited proteolysis coupled with mass spectrometry. The results showed that in case of TRPA1, irrespective of the ligand, the linker region and the N-terminal ankyrin repeats experience conformational changes leading to activation or inhibition of the channel.

Kruppel-Like Factor 2 Regulation of Aging and Healthspan: A Link Between the 3D Nucleome and Disease

Sweet, David Ryan Case Western Reserve University ProQuest Dissertat 2021 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

As modern medicine expands its reach, the downstream effects of successful medical intervention become realized. As many populations are beginning to experience an extension of healthy aging due to these interventions, there is increasingly greater understanding of diseases that preferentially impact aging individuals. At the heart all of these conditions are sustained or repetitive inflammation. While the cellular players in aging have been identified, molecular mechanisms regulating progression to disease remain to be discovered. Here, I describe insights into transcriptional regulators of inflammation that are implicated in aging and age-associated disease (AAD). Specifically, I explore the interplay between members of the Kruppel-like factor (KLF) family of transcription factors in the hemovascular system (i.e. endothelial and myeloid cells). First, I describe how two of these factors, KLF2 and KLF4, have evolved together in order to protect higher order organisms from aberrant activation of hemovascular cells. I then expand on the downstream consequences of this co-evolution in endothelial cells (ECs) by identifying novel mechanisms of long-range gene regulatory networks. Next, I make the case that inflammation resulting from KLF deletion is not all created equal. I demonstrate that although loss of KLF2 expression in myeloid cells worsens thrombotic disease, its downregulation may be critical for the vascular remodeling that occurs as a result. Long-term loss of KLF2 expression is nearly always detrimental as is discussed in chapters exploring the role of KLF2 in regulating metabolic disease and AADs. Outside of specific disease, KLF2 loss can also drive intrinsic aging processes which I describe in the context of a novel model for immunometabolic regulation of aging. Finally, I attempt to make the case that the diverse and robust phenotypes that occur due to loss of myeloid KLF2 are, in part, due to previously unappreciated genome-wide regulatory mechanisms. In particular, KLF2 maintains chromatin architecture critical for maintaining macrophage quiescence. Broadly, this work explores the fascinating world of inflammatory biology through the lens of KLF-driven transcriptional networks and how finding the delicate balance of immune and vascular cell activation may prove to be a viable option for targeting aging and AADs.

Sequential Monte Carlo for Estimating Brain Activity from MEG Data

Yu, Lijun Case Western Reserve University ProQuest Dissertat 2016 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Magnetoencephalography (MEG) is a noninvasive functional brain imaging technique with excellent temporal resolution. However, the magnetic field detected by the MEG instrument could be severely contaminated by both external and internal magnetic perturbations, particularly the spontaneous brain wave, leading to substantial challenges in the MEG inverse problem of the source localization. We treat the source localization problem in the Bayesian framework by utilizing Bayesian filtering methods. To address the dynamic influence of the background brain noise, we consider its spatio-temporal structure and a dynamic estimation model, used in each time slice to assist the source localization. According to the number of activated dipole sources, we propose two single-dipole models and a multi-dipole model to sequentially reconstruct the dipoles, modeling the sources by ensemble Kalman filters (EnKF) and the noise by particle filter. In the single-dipole case, we develop two algorithms, a nonlinear ensemble Kalman filter (EnKF) and a derivative-free EnKF, and investigate the difference of their performance. In the multi-dipole case, only nonlinear EnKF is considered.Numerical experiments show that the novel models proposed in this thesis can be used to accurately localize the dipoles through moderate computational resources with a high resolution.

Plasma-enhanced Chemical Film Conversion (PECFC): A Metal Free, Low-temperature Approach to Synthesizing Continuous, Large Area Layered Material Films

Liu, Tianqi Case Western Reserve University ProQuest Dissertat 2019 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Thin films of crystalline materials are typically synthesized by thermally decomposing vapor precursors on a catalytic substrate. Plasmas enable the process temperature to be lowered by assisting in decomposition of the precursor molecule through gas-phase excitation as in the case of plasma-enhanced chemical vapor deposition (PECVD) and plasma-enhanced atomic layer deposition (PEALD). In this work, we develop another plasma-assisted approach to synthesizing thin films which we term plasma-enhanced chemical film conversion (PECFC). Molecular precursors are first prepared as a thin film on a substrate by solution methods, and subsequently converted by a combination of heating and plasma treatment. In comparison to other thin film growth techniques, our approach circumvents the adsorption step to promote nucleation and reduce substrate interactions, allowing direct growth on metal-free substrates which eliminates the need for transfer. Additionally, the approach is additive, reducing materials wastage and producing materials at the point-of-need including patterned structures.Two examples of thin film materials will be presented that demonstrate the capabilities of this synthesis approach: hexagonal boron nitride (h-BN) and molybdenum disulfide (MoS2), both of which are layered materials and can be produced atomically thin. To synthesize h-BN, a single-molecular precursor, ammonia borane, is initially prepared as a thin film by spray deposition, spin coating, or ink jet printing, and subsequently converted in a cold-wall reactor with a planar, atmospheric-pressure dielectric barrier discharge. We show that h-BN synthesized by this process can be integrated in two-dimensional (2D)-based field effect transistor (FET) devices and improve the mobility by up to 4 times over silicon dioxide. To synthesize MoS2, a similar approach of converting its corresponding single-molecule precursor, ammonium tetrathiomolybdate with a plasma has been studied. In this case, a single-step conversion leads to a rough, nanostructured film. Adding a second thermal annealing step produces a very smooth (RMS < 0.5 nm) and higher crystal quality film. We show that the nanostructured film can be implemented as an electrochemical electrode for the hydrogen evolution reaction (HER).

Who Is Talking with Whom? Community Policing and Inter-Agency Collaboration in a Rustbelt Secondary City: A Case Study

Melvin-Campbell, Kelly Marie Case Western Reserve University ProQuest Dissertat 2019 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Forces like deindustrialization and globalization have left many second-tier rustbelt cities struggling with decline in population and neighborhood conditions, which can paint a negative image of these cities. One way that communities are attempting to improve their image is through crime reduction via multi-agency collaborations, like community policing. Previous literature has identified successful and unsuccessful elements of inter-agency collaborations but much of this work has examined the relationship between community police, and social and mental health services. Neighborhood development corporations focus on economic development, blight, and community building, thus making an ideal partner for community police. Yet, collaboration between community policing and neighborhood development corporations specifically has been understudied. This case study utilizes content analysis of data from written documentation (grant proposals and neighborhood reports), semi-structured interviews with neighborhood residents, the police department, and the neighborhood development corporation, as well as participant observation in neighborhood meetings. It explores the working relationship between the Youngstown Police Department and the Youngstown Neighborhood Development Corporation in Youngstown, Ohio, to investigate what elements of that relationship were positive and negative; and identify how and in what way collaboration occurs. It examines the potential structural, social, or economic factors that affect community policing from multiple stakeholders. Finally, the project examines spacial dynamics within two Youngstown neighborhoods served by community police officers. Results showed three primary findings: (1) The collaboration between the community police and neighborhood development in Youngstown is multidimensional and synergistic; (2) There is a paradigm clash between the traditional and community policing models that can hinder efforts at crime reduction and neighborhood stabilization; and (3) Neighborhoods are areas of contested space between the residents and police leadership, and between law-abiding and non-law-abiding residents. These findings have significant implications for secondary cities pursuing a crime-reduction/economic development model of urban renewal. First, inter-agency collaborations with community police initiatives should formalize partnership with neighborhood development corporations. Second, intra- and inter-agency barriers to the community policing model can dilute the model. Second, neighborhood program development could strengthen the police-community relationship. The findings from this project inform prior research on community policing, inter-agency collaboration and urban spacial dynamics.

Permanent Magnets and Electromechanical Control Systems for Spectroscopy and Low Field Communication

Glickstein, Jarred S Case Western Reserve University ProQuest Dissertat 2022 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

This thesis shows that permanent magnets and electromechanical control systems can enable power-efficient, high-sensitivity, low-noise modalities for spectroscopy and wireless communication. Specifically I present two examples. The first is a radio frequency (RF) spectrometer which uses a detector cooled to 77 K to maximize measurement sensitivity, coupled with a minimally-intrusive network of active duplexers and mechanical contact switches to realize a reconfigurable series/parallel resonant network. I present a receiver which combines the highly sensitive analog frontend instrumentation with a mixed signal embedded system to monitor and control secondary processes. The cryogenic system increases the measurement signal to noise ratio (SNR) by a factor of 10x.The second example is an extremely low frequency (ELF) communication system which uses a mechanically-rotated dipole instead of an electrical antenna to generate the oscillating field of the transmitter. I show how a synchronous digital controller can maintain stable control over the dynamic process while a complementary embedded system modulates the set-point and monitors the channel. My transmitter achieves a power efficiency 7.6? greater than an equivalent electrical antenna in a device small enough to be moved by one person. I carrythe transmitter into a cave and demonstrate cave-to-surface message transmission through 15 m of rock and frozen soil in a real-world field test.I present each solution in the context of scientific and human motivation, and explore tradeoffs required to achieve design goals. Emphasis is also placed on whether there exists a position of harmony and balance, where one may reasonably proclaim the optimum implementation has been achieved. The receiver is relatively more complex than the transmitter in the case of RF spectroscopy. In the case of ELF communication it is the reverse.

Soft Surface Grasping: Radular Opening in Aplysia californica

Kehl, Catherine E Case Western Reserve University ProQuest Dissertat 2019 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Grasping objects of differing shapes, sizes and material properties is a challenge both for biological and engineered systems. Many animals have adaptations that allow them to meet this challenge. The feeding system of Aplysia californica, a marine mollusk, is of particular interest because it is able to manipulate a wide variety of different sizes, textures and tensile strengths of macroalgaes. The grasping surface of Aplysia’s feeding organ, known as the radula, is a flexible surface covered with fine cartilaginous teeth. Previous in vitro work attributed opening of the grasper to the I7 muscle, a fine muscle located deep in the grasper. Lesion studies in vivo did show a reduction in the size of openings, but openings persisted, and animals were able to feed. In order to perform these in vivo studies a novel surgical technique was developed to access the I7 muscle, and a biologically balanced diverse aquarium environment was created to ensure the long term health of the animals over the length of the study. New in vitro studies identified a new set of muscular fibers on the underside of the radular surface, the sub-radular fibers (SRFs) as contributing to the conformational change in the radular surface that creates openings. Further in vivo studies found that lesioning these fibers leads to substantial decreases in opening width and in the ability of animals to ingest food. A theoretical biomechical model was created to suggest a mode of action for how these sub-radular fibers contract to create arched, rounded openings that could conform and envelop foodstuffs of a variety of different shapes. A three dimensional computational model, based on magnetic resonance imaging of intact behaving animals, and anatomical studies, provides support for the biomechanical model. These results demonstrate both a novel biomechanical mechanism, and suggest designs for creating soft robotic devices.