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- Genre: Doctoral Dissertation
Description
Single-cell proteomics and transcriptomics analysis are crucial to gain insights of
healthy physiology and disease pathogenesis. The comprehensive profiling of biomolecules in individual cells of a heterogeneous system can provide deep insights into many important biological questions, such as the distinct cellular compositions or regulation of inter- and intracellular signaling pathways of healthy and diseased tissues. With multidimensional molecular imaging of many different biomarkers in patient biopsies, diseases can be accurately diagnosed to guide the selection of the ideal treatment.
As an urgent need to advance single-cell analysis, imaging-based technologies have been developed to detect and quantify multiple DNA, RNA and protein molecules in single cell in situ. Novel fluorescent probes have been designed and synthesized, which targets specifically either their nucleic acid counterpart or protein epitopes. These highly multiplexed imaging-based platforms have the potential to detect and quantify 100 different protein molecules and 1000 different nucleic acids in a single cell.
Using novel fluorescent probes, a large number of biomolecules have been detected and quantified in formalin-fixed paraffin-embedded (FFPE) brain tissue at single-cell resolution. By studying protein expression levels, neuronal heterogeneity has been revealed in distinct subregions of human hippocampus.
healthy physiology and disease pathogenesis. The comprehensive profiling of biomolecules in individual cells of a heterogeneous system can provide deep insights into many important biological questions, such as the distinct cellular compositions or regulation of inter- and intracellular signaling pathways of healthy and diseased tissues. With multidimensional molecular imaging of many different biomarkers in patient biopsies, diseases can be accurately diagnosed to guide the selection of the ideal treatment.
As an urgent need to advance single-cell analysis, imaging-based technologies have been developed to detect and quantify multiple DNA, RNA and protein molecules in single cell in situ. Novel fluorescent probes have been designed and synthesized, which targets specifically either their nucleic acid counterpart or protein epitopes. These highly multiplexed imaging-based platforms have the potential to detect and quantify 100 different protein molecules and 1000 different nucleic acids in a single cell.
Using novel fluorescent probes, a large number of biomolecules have been detected and quantified in formalin-fixed paraffin-embedded (FFPE) brain tissue at single-cell resolution. By studying protein expression levels, neuronal heterogeneity has been revealed in distinct subregions of human hippocampus.
ContributorsMondal, Manas (Author) / Guo, Jia (Thesis advisor) / Gould, Ian (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2018
Description
Cadmium Telluride (CdTe) possesses preferable optical properties for photovoltaic (PV) applications: a near optimum bandgap of 1.5 eV, and a high absorption coefficient of over 15,000 cm-1 at the band edge. The detailed-balance limiting efficiency is 32.1% with an open-circuit voltage (Voc) of 1.23 V under the AM1.5G spectrum. The record polycrystalline CdTe thin-film cell efficiency has reached 22.1%, with excellent short-circuit current densities (Jsc) and fill-factors (FF). However, the Voc (~900 mV) is still far below the theoretical value, due to the large non-radiative recombination in the polycrystalline CdTe absorber, and the low-level p-type doping.
Monocrystalline CdTe/MgCdTe double-heterostructures (DHs) grown on lattice-matched InSb substrates have demonstrated impressively long carrier lifetimes in both unintentionally doped and Indium-doped n-type CdTe samples. The non-radiative recombination inside of, and at the interfaces of the CdTe absorbers in CdTe/MgCdTe DH samples has been significantly reduced due to the use of lattice-matched InSb substrates, and the excellent passivation provided by the MgCdTe barrier layers. The external luminescent quantum efficiency (η_ext) of n-type CdTe/MgCdTe DHs is up to 3.1%, observed from a 1-µm-thick CdTe/MgCdTe DH doped at 1017 cm-3. The 3.1% η_ext corresponds to an internal luminescent quantum efficiency (η_int) of 91%. Such a high η_ext gives an implied Voc, or quasi-Fermi-level splitting, of 1.13 V.
To obtain actual Voc, the quasi-Fermi-level splitting should be extracted to outside the circuit using a hole-selective contact layer. However, CdTe is difficult to be doped p-type, making it challenging to make efficient PN junction CdTe solar cells. With the use of MgCdTe barrier layers, the hole-contact layer can be defective without affecting the voltage. P-type hydrogenated amorphous silicon is an effective hole-selective contact for CdTe solar cells, enabling monocrystalline CdTe/MgCdTe DH solar cells to achieve Voc over 1.1 V, and a maximum active area efficiency of 18.8% (Jsc = 23.3 mA/cm2, Voc = 1.114 V, and FF = 72.3%). The knowledge gained through making the record-efficiency monocrystalline CdTe cell, particularly the n-type doping and the double-heterostructure design, may be transferable to polycrystalline CdTe thin-film cells and improve their competitiveness in the PV industry.
Monocrystalline CdTe/MgCdTe double-heterostructures (DHs) grown on lattice-matched InSb substrates have demonstrated impressively long carrier lifetimes in both unintentionally doped and Indium-doped n-type CdTe samples. The non-radiative recombination inside of, and at the interfaces of the CdTe absorbers in CdTe/MgCdTe DH samples has been significantly reduced due to the use of lattice-matched InSb substrates, and the excellent passivation provided by the MgCdTe barrier layers. The external luminescent quantum efficiency (η_ext) of n-type CdTe/MgCdTe DHs is up to 3.1%, observed from a 1-µm-thick CdTe/MgCdTe DH doped at 1017 cm-3. The 3.1% η_ext corresponds to an internal luminescent quantum efficiency (η_int) of 91%. Such a high η_ext gives an implied Voc, or quasi-Fermi-level splitting, of 1.13 V.
To obtain actual Voc, the quasi-Fermi-level splitting should be extracted to outside the circuit using a hole-selective contact layer. However, CdTe is difficult to be doped p-type, making it challenging to make efficient PN junction CdTe solar cells. With the use of MgCdTe barrier layers, the hole-contact layer can be defective without affecting the voltage. P-type hydrogenated amorphous silicon is an effective hole-selective contact for CdTe solar cells, enabling monocrystalline CdTe/MgCdTe DH solar cells to achieve Voc over 1.1 V, and a maximum active area efficiency of 18.8% (Jsc = 23.3 mA/cm2, Voc = 1.114 V, and FF = 72.3%). The knowledge gained through making the record-efficiency monocrystalline CdTe cell, particularly the n-type doping and the double-heterostructure design, may be transferable to polycrystalline CdTe thin-film cells and improve their competitiveness in the PV industry.
ContributorsZhao, Yuan (Author) / Zhang, Yong-Hang (Thesis advisor) / Bertoni, Mariana (Committee member) / King, Richard (Committee member) / Holman, Zachary (Committee member) / Arizona State University (Publisher)
Created2016
Description
This action research study is a mixed methods investigation of doctoral students’ preparedness for multiple career paths. PhD students face two challenges preparing for multiple career paths: lack of preparation and limited engagement in conversations about the value of their research across multiple audiences. This study focuses on PhD students’ perceived perception of communicating the value of their research across academic and non-academic audiences and on an institutional intervention designed to increase student’s proficiency to communicate the value of their PhD research across multiple audiences. Additionally, the study identified ways universities can implement solutions to prepare first-generation PhD students to effectively achieve their career goals.
I developed a course titled Preparing Future Scholars (PFS). PFS was designed to be an institutional intervention to address the fundamental changes needed in the career development of PhD students. Through PFS curricula, PhD students engage in conversations and have access to resources that augment both the traditional PhD training and occupational identity of professorate. The PFS course creates fundamental changes by drawing from David Kolb’s Experiential Learning Theory and the Social Cognitive Career Theory (SCCT) developed by Robert Lent, Steven Brown, and Gail Hackett. The SCCT looks at one’s self-efficacy beliefs, outcome expectations, goal representation, and the interlocking process of interest development, along with their choice and performance.
I used a concurrent triangulation mixed methods research model that included collecting qualitative and quantitative data over 8 weeks. The results of the study indicated that PhD students’ career preparation should focus on articulating the relevancy of their research across academic and non-academic employment sectors. Additionally, findings showed that PhD students’ perception of their verbal and non-verbal skills to communicate the value of their research to both lay and discipline specific audiences were not statistically different across STEM and non-STEM majors, generational status, or gender, but there are statistical differences within each group. PhD programs provide students with the opportunity to cultivate intellectual knowledge, but, as this study illustrates, students would also benefit from the opportunity to nurture and develop practical knowledge and turn “theory into practice.”
I developed a course titled Preparing Future Scholars (PFS). PFS was designed to be an institutional intervention to address the fundamental changes needed in the career development of PhD students. Through PFS curricula, PhD students engage in conversations and have access to resources that augment both the traditional PhD training and occupational identity of professorate. The PFS course creates fundamental changes by drawing from David Kolb’s Experiential Learning Theory and the Social Cognitive Career Theory (SCCT) developed by Robert Lent, Steven Brown, and Gail Hackett. The SCCT looks at one’s self-efficacy beliefs, outcome expectations, goal representation, and the interlocking process of interest development, along with their choice and performance.
I used a concurrent triangulation mixed methods research model that included collecting qualitative and quantitative data over 8 weeks. The results of the study indicated that PhD students’ career preparation should focus on articulating the relevancy of their research across academic and non-academic employment sectors. Additionally, findings showed that PhD students’ perception of their verbal and non-verbal skills to communicate the value of their research to both lay and discipline specific audiences were not statistically different across STEM and non-STEM majors, generational status, or gender, but there are statistical differences within each group. PhD programs provide students with the opportunity to cultivate intellectual knowledge, but, as this study illustrates, students would also benefit from the opportunity to nurture and develop practical knowledge and turn “theory into practice.”
ContributorsCason, Jennifer (Author) / Liou, Daniel (Thesis advisor) / Barber, Rebecca (Committee member) / Justice, George (Committee member) / Schugurensky, Daniel, 1958- (Committee member) / Arizona State University (Publisher)
Created2016
Description
Exome sequencing was used to identify novel variants linked to amyotrophic lateral sclerosis (ALS), in a family without mutations in genes previously linked to ALS. A F115C mutation in the gene MATR3 was identified, and further examination of other ALS kindreds identified an additional three mutations in MATR3; S85C, P154S and T622A. Matrin 3 is an RNA/DNA binding protein as well as part of the nuclear matrix. Matrin 3 interacts with TDP-43, a protein that is both mutated in some forms of ALS, and found in pathological inclusions in most ALS patients. Matrin 3 pathology, including mislocalization and rare cytoplasmic inclusions, was identified in spinal cord tissue from a patient carrying a mutation in Matrin 3, as well as sporadic ALS patients. In an effort to determine the mechanism of Matrin 3 linked ALS, the protein interactome of wild-type and ALS-linked MATR3 mutations was examined. Immunoprecipitation followed by mass spectrometry experiments were performed using NSC-34 cells expressing human wild-type or mutant Matrin 3. Gene ontology analysis identified a novel role for Matrin 3 in mRNA transport centered on proteins in the TRanscription and EXport (TREX) complex, known to function in mRNA biogenesis and nuclear export. ALS-linked mutations in Matrin 3 led to its re-distribution within the nucleus, decreased co-localization with endogenous Matrin 3 and increased co-localization with specific TREX components. Expression of disease-causing Matrin 3 mutations led to nuclear mRNA export defects of both global mRNA and more specifically the mRNA of TDP-43 and FUS. Our findings identify ALS-causing mutations in the gene MATR3, as well as a potential pathogenic mechanism attributable to MATR3 mutations and further link cellular transport defects to ALS.
ContributorsBoehringer, Ashley (Author) / Bowser, Robert (Thesis advisor) / Liss, Julie (Committee member) / Jensen, Kendall (Committee member) / Ladha, Shafeeq (Committee member) / Arizona State University (Publisher)
Created2018
Description
Understanding where our bodies are in space is imperative for motor control, particularly for actions such as goal-directed reaching. Multisensory integration is crucial for reducing uncertainty in arm position estimates. This dissertation examines time and frequency-domain correlates of visual-proprioceptive integration during an arm-position maintenance task. Neural recordings were obtained from two different cortical areas as non-human primates performed a center-out reaching task in a virtual reality environment. Following a reach, animals maintained the end-point position of their arm under unimodal (proprioception only) and bimodal (proprioception and vision) conditions. In both areas, time domain and multi-taper spectral analysis methods were used to quantify changes in the spiking, local field potential (LFP), and spike-field coherence during arm-position maintenance.
In both areas, individual neurons were classified based on the spectrum of their spiking patterns. A large proportion of cells in the SPL that exhibited sensory condition-specific oscillatory spiking in the beta (13-30Hz) frequency band. Cells in the IPL typically had a more diverse mix of oscillatory and refractory spiking patterns during the task in response to changing sensory condition. Contrary to the assumptions made in many modelling studies, none of the cells exhibited Poisson-spiking statistics in SPL or IPL.
Evoked LFPs in both areas exhibited greater effects of target location than visual condition, though the evoked responses in the preferred reach direction were generally suppressed in the bimodal condition relative to the unimodal condition. Significant effects of target location on evoked responses were observed during the movement period of the task well.
In the frequency domain, LFP power in both cortical areas was enhanced in the beta band during the position estimation epoch of the task, indicating that LFP beta oscillations may be important for maintaining the ongoing state. This was particularly evident at the population level, with clear increase in alpha and beta power. Differences in spectral power between conditions also became apparent at the population level, with power during bimodal trials being suppressed relative to unimodal. The spike-field coherence showed confounding results in both the SPL and IPL, with no clear correlation between incidence of beta oscillations and significant beta coherence.
In both areas, individual neurons were classified based on the spectrum of their spiking patterns. A large proportion of cells in the SPL that exhibited sensory condition-specific oscillatory spiking in the beta (13-30Hz) frequency band. Cells in the IPL typically had a more diverse mix of oscillatory and refractory spiking patterns during the task in response to changing sensory condition. Contrary to the assumptions made in many modelling studies, none of the cells exhibited Poisson-spiking statistics in SPL or IPL.
Evoked LFPs in both areas exhibited greater effects of target location than visual condition, though the evoked responses in the preferred reach direction were generally suppressed in the bimodal condition relative to the unimodal condition. Significant effects of target location on evoked responses were observed during the movement period of the task well.
In the frequency domain, LFP power in both cortical areas was enhanced in the beta band during the position estimation epoch of the task, indicating that LFP beta oscillations may be important for maintaining the ongoing state. This was particularly evident at the population level, with clear increase in alpha and beta power. Differences in spectral power between conditions also became apparent at the population level, with power during bimodal trials being suppressed relative to unimodal. The spike-field coherence showed confounding results in both the SPL and IPL, with no clear correlation between incidence of beta oscillations and significant beta coherence.
ContributorsVanGilder, Paul (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Muthuswamy, Jit (Committee member) / Foldes, Stephen (Committee member) / Arizona State University (Publisher)
Created2017
Description
The human hand is a complex biological system. Humans have evolved a unique ability to use the hand for a wide range of tasks, including activities of daily living such as successfully grasping and manipulating objects, i.e., lifting a cup of coffee without spilling. Despite the ubiquitous nature of hand use in everyday activities involving object manipulations, there is currently an incomplete understanding of the cortical sensorimotor mechanisms underlying this important behavior. One critical aspect of natural object grasping is the coordination of where the fingers make contact with an object and how much force is applied following contact. Such force-to-position modulation is critical for successful manipulation. However, the neural mechanisms underlying these motor processes remain less understood, as previous experiments have utilized protocols with fixed contact points which likely rely on different neural mechanisms from those involved in grasping at unconstrained contacts. To address this gap in the motor neuroscience field, transcranial magnetic stimulation (TMS) and electroencephalography (EEG) were used to investigate the role of primary motor cortex (M1), as well as other important cortical regions in the grasping network, during the planning and execution of object grasping and manipulation. The results of virtual lesions induced by TMS and EEG revealed grasp context-specific cortical mechanisms underlying digit force-to-position coordination, as well as the spatial and temporal dynamics of cortical activity during planning and execution. Together, the present findings provide the foundation for a novel framework accounting for how the central nervous system controls dexterous manipulation. This new knowledge can potentially benefit research in neuroprosthetics and improve the efficacy of neurorehabilitation techniques for patients affected by sensorimotor impairments.
ContributorsMcGurrin, Patrick M (Author) / Santello, Marco (Thesis advisor) / Helms-Tillery, Steve (Committee member) / Kleim, Jeff (Committee member) / Davare, Marco (Committee member) / Arizona State University (Publisher)
Created2017
Description
Data and the use of data to make educational decisions have attained new-found prominence in K-12 education following the inception of high-stakes testing and subsequent linking of teacher evaluations and teacher-performance pay to students' outcomes on standardized assessments. Although the research literature suggested students' academic performance benefits were derived from employing data-informed decision making (DIDM), many educators have not felt efficacious about implementing and using DIDM practices. Additionally, the literature suggested a five-factor model of teachers' efficacy and anxiety with respect to using DIDM practices: (a) identification of relevant information, (b) interpretation of relevant information, (c) application of interpretations of data to their classroom practices, (d) requisite technological skills, and (e) comfort with data and statistics.
This action research study was designed to augment a program of support focused on DIDM, which was being offered at a K-8 charter school in Arizona. It sought to better understand the relation between participation in professional development (PD) modules and teachers' self-efficacy for using DIDM practices. It provided an online PD component, in which 19 kindergarten through 8th-grade teachers worked through three self-guided online learning modules, focused sequentially on (a) identification of relevant student data, (b) interpretation of relevant student data, and (c) application of interpretations of data to classroom practices. Each module concluded with an in-person reflection session, in which teachers shared artifacts they developed based on the modules, discussed challenges, shared solutions, and considered applications to their classrooms.
Results of quantitative data from pre- and post-intervention assessments, suggested the intervention positively influenced participants' self-efficacy for (a) identifying and (b) interpreting relevant student data. Qualitative results from eight semi-structured interviews conducted at the conclusion of the intervention indicated that teachers, regardless of previous experience using data, viewed DIDM favorably and were more able to find and draw conclusions from their data than they were prior to the intervention. The quantitative and qualitative data exhibited complementarity pointing to the same conclusions. The discussion focused on explaining how the intervention influenced participants' self-efficacy for using DIDM practices, anxiety around using DIDM practices, and use of DIDM practices.
This action research study was designed to augment a program of support focused on DIDM, which was being offered at a K-8 charter school in Arizona. It sought to better understand the relation between participation in professional development (PD) modules and teachers' self-efficacy for using DIDM practices. It provided an online PD component, in which 19 kindergarten through 8th-grade teachers worked through three self-guided online learning modules, focused sequentially on (a) identification of relevant student data, (b) interpretation of relevant student data, and (c) application of interpretations of data to classroom practices. Each module concluded with an in-person reflection session, in which teachers shared artifacts they developed based on the modules, discussed challenges, shared solutions, and considered applications to their classrooms.
Results of quantitative data from pre- and post-intervention assessments, suggested the intervention positively influenced participants' self-efficacy for (a) identifying and (b) interpreting relevant student data. Qualitative results from eight semi-structured interviews conducted at the conclusion of the intervention indicated that teachers, regardless of previous experience using data, viewed DIDM favorably and were more able to find and draw conclusions from their data than they were prior to the intervention. The quantitative and qualitative data exhibited complementarity pointing to the same conclusions. The discussion focused on explaining how the intervention influenced participants' self-efficacy for using DIDM practices, anxiety around using DIDM practices, and use of DIDM practices.
ContributorsNelson, Andrew (Author) / Buss, Ray R (Thesis advisor) / Preach, Deborah (Committee member) / Buchanan, James (Committee member) / Mertler, Craig A. (Committee member) / Arizona State University (Publisher)
Created2017
Description
The issue of teacher shortages has been a national crisis in the United States. Teachers have expressed feeling exhausted and burnt out from the profession. The COVID-19 pandemic made these feelings worse, with the rates of teachers leaving the profession being higher than what has occurred in the past. Teachers’ sense of belonging at their schools and their professional identities as educators can have an impact on their decisions to stay in or leave the field of education. Participation in a community of practice has been shown to have a positive impact on teachers’ sense of belonging and identities. This qualitative study cultivated a community of practice composed of teachers who were new to their schools but not necessarily new to teaching. Data collected included interviews, recordings of community of practice meetings, participant reflection documents, and a researcher journal. Results suggested that teachers valued getting to know their colleagues, learning unique classroom practices, and that their participation in the community of practice had a positive impact on their sense of belonging at their new schools. The impacts of the community of practice on teachers’ professional identities were inconclusive. The discussion included an analysis of themes that emerged from the data, limitations of the study, and recommendations for researchers and practitioners.
ContributorsTarbutton, Taylor Lane (Author) / Judson, Eugene (Thesis advisor) / Frias, Elizabeth (Thesis advisor) / Weber, Steven (Committee member) / Arizona State University (Publisher)
Created2023
Description
In an era of educational transformation, teacher leaders play a pivotal role in facilitating systemic change within schools. This dissertation presents a single-case action research study investigating the support structures provided by a Team Lead Communities of Practice (TL CoP) to nurture teacher leaders. The primary aim of this research is to explore the effectiveness of the TL CoP in supporting teacher leaders at one school site. Utilizing qualitative data from interviews, participant journals, researcher memos, and agendas, this study captures the perspectives of team leads of interdisciplinary teams. The findings emphasize the need for flexible support systems tailored to the unique challenges teacher leaders face. Offering teacher leaders agency in their learning is paramount to their success. Additionally, structured time for collaboration and problem-solving within the TL CoP is crucial. One significant revelation is the importance of role clarity. Team leads need a clear understanding of their responsibilities to effectively lead teams and drive systemic change. This research contributes to the literature on educational leadership by highlighting the vital role of teacher leaders and the potential of TL CoPs in supporting their development. It advocates for the creation of such communities as a promising strategy to empower teacher leaders, providing them with essential support, dedicated collaboration time, and role clarity. As schools evolve to meet the demands of the 21st century, the insights from this study offer guidance for educational stakeholders seeking to cultivate a culture of leadership and foster systemic change through teacher leadership.
ContributorsPreston, Lee Allyne Cox (Author) / Markos, Amy (Thesis advisor) / Corner, Kevin (Committee member) / Fourlis, Andi (Committee member) / Arizona State University (Publisher)
Created2023