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Targeting Mechanisms of Resistance to Endocrine Therapy in Combination with CDK4/6 Inhibitors in ER+ Metastatic Breast Cancer
No full textThis work is embargoed by the author and will not be publicly available until May 2034.Despite the great success of the selective CDK4/6 inhibitors in treating Estrogen receptor positive (ER)+/ HER2- metastatic breast cancer (MBC), acquired and intrinsic resistance remain inevitable. To date, there are no known reliable biomarkers for predicting treatment response or to redirect therapy and overcome resistance to CDK4/6 inhibitors in the clinic. Preliminary findings collected by the Side Out 3 (SO3) trial (ClinicalTrials.gov ID: NCT03195192), a clinical study aiming at identifying predictive markers of response to endocrine therapy (ET) in combination with CDK4/6 inhibitors, showed that increased expression of the epigenetic regulator EZH2 was associated with lack of response to treatment. Using a combination of observational and mechanistic approaches, this study aimed at understanding the role of EZH2 in the development of resistance to CDK 4/6 inhibitors in ER+/HER2- metastatic breast cancer and exploring its potential as a therapeutic target to redirect treatment. To investigate EZH2 role, isogenic ER+/HER2- breast cancer model systems with stable acquired resistance to CDK4/6 inhibitors palbociclib and abemaciclib were developed. To determine if EZH2 expression alone is sufficient to modulate response to CDK 4/6 inhibition, EZH2 overexpression was induced in non-resistant cells through lentivirus transduction. To assess EZH2 therapeutic potential, EZH2 was knocked down in CDK4/6 resistant cell lines with shRNA transfection and response to treatment with two EZH2 inhibitors, Tazemetostat and MS1943, was compared across parental and resistant cell lines in 2D and 3D culture. Taken together, our data suggest that EZH2 may represent a new therapeutic target in ER+/HER2- MBCs that are resistant to CDK 4/6 inhibition in combination with ET. Our data also indicate that resistance to treatment may be driven through EZH2 non-canonical activities opening new opportunities for developing new precision targeted approach for MBC patients.2034-05-1
Memory Politics and Building Multinational States in Africa: Collective Memory, Identity Conflict, and Constitution Making in Ethiopia
No full textThis work is embargoed by the author and will not be publicly available until May 2029.The dissertation “Memory Politics and Building Multinational States in Africa: Collective Memory, Identity Conflict, and Constitution Making in Ethiopia” investigates the complex interplay between collective memory and identity conflicts in shaping the constitutional framework in Ethiopia, a key example of a multinational state in Africa. This study focuses on how varying interpretations and narratives of collective memory influence ethnic and political dynamics, affecting both national narratives and internal conflicts. It particularly examines the role of these collective memories in the constitutional making process, assessing how Ethiopia's diverse ethnic and cultural identities are represented and managed within the 1995 Federal constitution. Employing both theoretical analysis and empirical research, including interviews and constitutional document analysis, this research provides insightful contributions to the understanding of nation-building in Africa, underlining the significant impact of memory politics and identity in the formation and functioning of multinational states.2029-05-1
SMART CITIES AND A MODERN APPROACH TO STRUCTURAL HEALTH MONITORING: AUTONOMOUS VISUAL SENSING AND DECISION MAKING
Full text linkA smart city, in the context of infrastructure, can be defined as an urban area utilizing diverse sensing systems for autonomous data collection, processing, and decision-making to ensure safety, serviceability, and resiliency. Large-scale machine vision approaches recently emerged as a preferable alternative for achieving autonomy in data acquisition and processing, surpassing conventional structural sensing methods. This dissertation offers insights into an integrated infrastructure monitoring and operations framework for a smart city, focusing on machine vision-based data acquisition and denoising. Four key aspects are explored. Firstly, the research investigates vision-based data collection as a practical structural health monitoring (SHM) sensing approach. Techniques for vision-based response measurement are studied and compared in field setups, quantifying their efficiency by contrasting results with those recorded by conventional sensors. Secondly, the study explores the utilization of redundancies present in signals coming from different vison-based displacement measurement techniques and the use of a deep learning-based data fusion approach to enhance the signal-to-noise ratio (SNR) in measurements. The third study addresses challenges introduced when mounting a digital camera on an unmanned aerial vehicle (UAV), creating additional relative displacements. An approach utilizing a 3D targeting system in combination with camera pose estimation is developed and tested in lab and field experiments. The final part is focused on the fundamental concepts of ontology and its potential applications, discussing how ontology facilitates sensor data flow and its integration, structural data modeling, and knowledge sharing in SHM systems. A sample ontological model showcases the potential of using ontology to realize the digital twin concept for SHM in a smart city
Exploring Special Education Teacher and Teacher Educator Perceptions of the Standard Outcome Lesson and Reflection Guide to Support Curriculum Mapping
Full text linkThe purpose of this study is to explore special education teacher and teacher educator perceptions of the Standard Outcome Lesson and Reflection (SOLAR) Guide. Even though research shows that special education teachers need the skill of curriculum mapping in their roles in the classroom, a dearth of research has identified effective ways to help special education teachers with this process. Tables of specification have been identified as a potential resource to support special education teachers, however, this study is among the first studies to leverage tables of specification in a tangible resource called the SOLAR Guide to help special education teachers navigate curriculum mapping. The SOLAR Guide was designed to support curriculum mapping by having special education teachers systematically and purposefully align content standards, assessments, lessons, and evidence-based instructional strategies in secondary general education content classes. The design of the SOLAR Guide followed the process of educational design research. Educational design research allowed for an iterative and collaborative process that incorporated special education induction year teacher feedback into the SOLAR Guide. Perceptions of the SOLAR Guide were explored through interviews of teachers and teacher educators, a feedback questionnaire, and samples of completed guides. The findings of this study suggest that (a) special education induction year teachers and teacher educators saw the same potential in the SOLAR Guide as a visual aid, collaborative document, and reflective tool to support curriculum mapping (b) special education induction year teachers and teacher educators used similar language related to movement when describing how they conceptualized the mapping and teaching of a curriculum (c) special education induction year teachers and teacher educators saw potential in adoption of the SOLAR Guide in special education teacher preparation programs and made recommendations for its future adoption and use (d) special education induction year teachers and teacher educators identified limitations of the SOLAR Guide and barriers to its adoption. A comprehensive discussion of the findings, implications for future use of the SOLAR Guide and future directions for research are offered
MACHINE LEARNING THAT MAKES SENSE IN CLINICAL SETTINGS
Full text linkThis dissertation aimed to explore the use of machine learning (ML) models in in-patient clinical settings. A literature review was conducted to identify existing guidelines and frameworks for such models, and an in-depth study was conducted on ML-based models to understand their behavior and implications on patient outcomes. A conceptual framework was developed for the structure, components, steps, and considerations necessary for an ML-based model to make sense in a clinical setting, and an ontology-guided representation of the framework was discussed. Additionally, the dissertation discusses the performance evaluation of ML models in supervised learning using time-stamped clinical data and proposed a clinically relevant temporal evaluation method
Examining the Functional Relation between Variations of a Multicomponent Literacy Intervention and Improvements in Foundational Reading Skills by Young Students with Down Syndrome
Full text linkChildren with Down syndrome exhibit unique learning characteristics that impact their educational progress. Despite this, research on effective reading interventions specifically tailored for this population remains limited. The present study aimed to find the best ways to teach teaching foundational reading skills to children with Down syndrome. Specifically, the focus was on letter-sound correspondence and the ability to identify initial sounds using pictures. Additionally, the study explored whether modifications aligned with the Down syndrome behavioral phenotype could enhance learning outcomes. Adapted versions of the Early Literacy Skills Builder (ELSB) curriculum were employed to further support children with Down syndrome. The research design utilized a single-case multiple-baseline approach across four participants in kindergarten through second grade. These participants were at the early stages of reading development and primarily communicated verbally. Despite variability and mixed trends observed during different phases, the results revealed moderate evidence of a functional relation between the ELSB: Basic Strategies version of the curriculum and the targeted reading skills. The social validity of the intervention was supported by the participants and parents reports of perceived importance and intentions to continue using the strategies. These findings hold implications for the design of effective reading interventions for children with Down syndrome and adapting existing curricula to meet their unique needs
Advanced Characterization of Gallium Oxide Field-Effect Transistors
Full text linkBeta-phase Gallium Oxide (β-Ga2O3) has garnered significant attention in the last 12 years as an ultra-wide bandgap semiconductor for high power applications. With breakdown electric fields and saturation velocities surpassing those of commercial wide bandgap semiconductors such as SiC and GaN, β-Ga2O3 boasts significantly larger theoretical figures of merit for both low and high frequency applications. However, high defect densities and limited understanding in their formation due to the complex atomic structure of β-Ga2O3 prevents achieving near-theoretical performance. Most device characterization methods have been developed for nominal bandgap materials such as Silicon, while novel techniques have been reported using illumination for deep-level defects in wide bandgap semiconductors such as GaN. Similarly, device-level characterization of defects is required for β-Ga2O3. In this thesis, we report on various characterization techniques performed on β-Ga2O3 lateral field-effect transistors (FETs) that highlight the reduction in device performance due to defects. In chapter 1, we discuss the progress in performance and defect characterization of β-Ga2O3 FETs. We also mention the next steps and challenges to commercialize β-Ga2O3. In chapter 3, we extract both channel and series resistances using a transfer-length method (TLM) applied on FETs with varying gate-drain spacings and observe an increase in series resistance with decreasing gate voltage. This is attributed to surface defects extending the depletion into the ungated region. In chapter 4, we use illumination in conjunction standard current-voltage and capacitance-voltage measurements to extract FET effective mobility curves with varying densities of filled deep-level traps. Using this method, we notice that defects 3.4 eV – 4.0 eV below the conduction band strongly scatter electrons and reduce the mobility by 30 % – 70 % with increasing distance between the channel and the gate oxide/semiconductor interface. Traps in other ranges, however, have minor changes on the mobility. Chapter 5 discusses the impact of slow traps on the reliability of gallium oxide lateral transistors. These are studied through pulsed I-V measurements. Pulsed FET transfer, ID-VGS, characteristics are measured using two types of pulses at multiple rise/fall times, and multiple stress times. Drain current reduction and field-effect mobility degradation highlight the instability observed in β-Ga2O3 FETs. Chapter 6 summarizes the research presented in this thesis and discusses plans for future work. An appendix is included at the end discussing measurements and simulations of GaN pn diodes
Ground-based Light Curve Follow-up Validation observations of TESS object of interest TOI 5191.01
Full text link“The goal of this observation was to confirm the presence of an exoplanet around TESS object of interest 5191.01. The NASA TESS mission first observed this stars potential exoplanet. Using the light curve method, the authors observed the star during the expected exoplanet transit. Unfortunately, the authors results were inconclusive due to data loss during the transit. Cloud cover caused the loss of data of the first half of the transit including the expected ingress of the exoplanet. This loss of data means the authors cannot say whether or not there is an exoplanet around TOI 5191.01 but preliminary data suggests there is potentially exoplanet around star TOI 5191.01, but more data will need to be collected because key data was lost due to cloud cover during the transit.
Ground-based Light Curve Follow-up Validation observations of TESS object of interest TOI 4064.01
Full text link“The TESS satellite scans the sky for possible exoplanets using the transit photometry method. From this initial observation, any possible exoplanet candidates are marked as objects of interest and selected for follow-up ground-based observations. This paper presents the results of follow-up ground-based observation conducted on the candidate exoplanet TOI 4064.01. The goal of this observation was to determine if the transit detected for TOI 4064.01 occurred near the predicted star at the expected time with the predicted duration and orbital depth. This process was accomplished using AstroImageJ to create and analyze the light curve. Observation data of TOI 4064.01 was obtained from the George Mason University 0.8m telescope and was plate-solved using AstroImageJ. After generating a light curve and performing an NEB check, it is inconclusive whether or not there is a transit. This study aims to provide a foundation for any future work that may be conducted on TOI 4064.01.
The Long-Run Effects of a Colonial Institution on Development and Political Economic Preferences: Evidence from Indonesia
Full text linkTaking advantage of a within-country variation that occurred in Indonesia during the country’s colonization by the Dutch, namely the development of a post road in Java in the early 19th century, this dissertation analyzes whether people who live nearer to the post road tend to have a higher level of economic development and stronger preferences for democracy and market economy compared to people who live in farther away areas. This dissertation finds that cities/regencies that are located closer to the post road tend to have higher development levels, but the people who live there do not show stronger preference for democracy although they do show a significantly stronger preference for market economy compared to people who live farther away from the road. The post road’s original purposes of improving Java’s transportation and communication networks for the Dutch military plausibly initiated the growths of trading and urbanization which eventually led to the increased welfare of societies near the road which then gradually spread into communities farther away. Having more opportunities of benefiting economically from the road may be the reason that people in areas nearer to the post road tend to show more acceptance toward market economy values. This dissertation also finds that regardless of their proximities to the road, democracy is highly preferred by majority of people across Java. However, further inspection shows that the people also generally have high preference for traditionalism values which are used as proxies for a feudalistic culture and generally are incompatible with democracy. This may be a reason to suspect that democracy in Indonesia is still vulnerable. This dissertation calls for more thorough investigations toward the role of enduring cultural traits and their effects on a society’s political economic preferences and suggests some follow-up research ideas building on its findings and elaborations