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TOWARDS VISION-GUIDED SKULL BASE SURGERY
No full textSkull base surgery is a complex procedure due to the critical anatomies only
millimeters away from the surgical field. Damaging these critical tissues can lead to
life-threatening surgical complications. The limited visibility further exacerbates the
situation as most of these tissues are hidden behind the bone. To improve surgical
safety and clinical outcome, a vision-based system is built to provide surgeons with
more context-situational awareness. The contributions of this dissertation include 1)
a set of computer vision algorithms that perform spatio-temporal reasoning of the
surgical scene, and 2) simulation technologies that enable advanced visualization of
the current surgical progress. The novel computer vision algorithms enable us to
perform depth estimation, motion tracking, and surface reconstruction. The simulation
technologies include virtual drilling software and a digital twin paradigm. Together,
these components build a synergistic ecosystem that has the potential to meet the
clinical accuracy requirements as it evolves
CULTIVATING STUDENT ENGAGEMENT AND ENHANCING TEACHING SELF-EFFICACY IN HIGHER EDUCATION STEM: A NEUROEDUCATION FRAMEWORK
No full textThere is a gender gap for women completing higher education science, technology, engineering, and mathematics (STEM) degrees, despite the greater percentage of women than men enrolled in college since 1981. This gap is exacerbated for minoritized women. STEM is known for the chilly climate for women and those outside the dominant culture. A lack of representation is partly to blame for the subtle and sometimes overt hostilities women face. An initial convergent parallel mixed-method needs assessment study indicated a significant difference along gender lines between how students and faculty perceived the level of student engagement. Faculty reported lower engagement for female students than males, while students reported no difference in cognitive engagement based on gender. This early research also showed that faculty used significantly more instructor-centered than student-centered instructional practices. This quasi-experimental convergent parallel mixed-methods study created a professional learning community for STEM faculty to increase teaching self-efficacy and student-centered practices. The brain-targeted teaching model was customized for higher education STEM and used. This study compared a non-STEM faculty control group with a STEM faculty treatment group. Post-test results showed significant increases in self-efficacy for the treatment group, both between groups and within the treatment group. The treatment group also showed a significant increase in efficacy for instructional strategies
CRISPR-Cas12a mediated combinatorial knock-out of multiple epigenetically silenced genes promotes pro-tumorigenic properties in colon cancer evolution
No full textGenome-wide epigenetic alterations are important for the development of cancers. In any given cancer tissue, multiple important developmental regulators undergo epigenetic silencing. Similar epigenetic alterations are observed in normal physiological aging. The cumulative effects of multiple epigenetically silenced genes (ESGs) on tumor development remains an unaddressed aspect of cancer biology, due to the lack of tools for targeting multiple genes, tractable biological models, and assays to measure tumor development. Here, we established a BrafV600E ¬driven ex vivo mouse proximal colon organoid model of colorectal cancer (CRC) to follow tumor progression and identify the effect of multiple ESGs on tumor progression. We used a class V CRISPR system that uses Cas12a to produce CRISPR RNA (crRNAs) targeting multiple ESGs from an array of precursor-crRNA (precrRNA). To address how genes altered by epigenetic changes cumulatively impact cancer initiation, genes undergoing simultaneous epigenetic silencing in human colon cancers were studied. We knocked out combinations of such genes using a newly designed CRISPR-Cas12a system. To use the system, our CRISPR arrays contained semi-random combinations of four guide RNAs. Organoids transduced with our combinatorial lentiviral library were screened for Wnt factor independent growth to assess tumorigenic potential. Combinatorial guide arrays were amplified from the organoids that were able to survive in Wnt factor deficient medium and subsequently sequenced. Overrepresented guide RNAs combinations were analyzed. We demonstrated that in comparison to individual gene knockout, targeted knockout of multiple ESGs in the Wnt and senescence pathways, including the key anti-differentiation gene Cdx2, in the organoids have synergistic effects on inducing Wnt-independent growth and tumor initiation. Inactivating multiple ESGs simultaneously in the absence of oncogene induction sufficiently increases stemness potential. Finally, in preliminary analyses, we identified combinations of guides, mainly driven by Cdx2 and Apc targeting, that provide Wnt independent growth. Our preliminary analyses suggest that functional screening by inactivation of multiple genes by CRISPR approaches can identify the role of simultaneous inactivation of multiple genes in the early stages of tumor development
PLK4 SELF-PHOSPHORYLATION DRIVES THE SELECTION OF A SINGLE SITE FOR PROCENTRIOLE ASSEMBLY
No full textCentrioles are cylindrical-shaped organelles that recruit a surrounding pericentriolar material (PCM) to form the centrosome, a microtubule-organizing center that arranges the interphase microtubule cytoskeleton and forms the poles of the mitotic spindle during cell division. Each dividing cell inherits a single centrosome from a previous division, but two are required to build the bipolar mitotic spindle successfully. As a single pair of centrioles exists as the core of the centrosome, centriole copy number is directly regulated to ensure faithful cell division. Therefore, each centriole within the pair must duplicate only once every cell cycle. Centriole duplication occurs in S-phase and is regulated by Polo-like kinase 4 (PLK4). How PLK4 selects a single site on parent centrioles for procentriole assembly remains unclear.
As centrioles are near the resolution limit of traditional widefield microscopes, studying changes in PLK4 localization has been challenging. To circumvent this, we utilized ultrastructure expansion microscopy (U-ExM) to physically expand centrioles ~4x isotropically and show that PLK4 localizes at discrete sites along the wall of parent centrioles. While there is variation in the number of sites PLK4 occupies, most PLK4 localizes at a dominant site on parent centrioles that directs procentriole assembly. Inhibition of PLK4 stabilizes its binding at the centriole and increases occupancy to a maximum of nine sites, which mirrors the inherent nine-fold rotational symmetry of the centriole.
PLK4 kinase activity promotes the release of active PLK4 from the centriole and drives drive the selection of a single site for procentriole assembly. PLK4 self- phosphorylates ten sites along a flexible linker to promote release. Preventing linker phosphorylation through mutation blocks PLK4 turnover, leading to supernumerary sites of PLK4 localization and centriole amplification. Therefore, self-phosphorylation is a major driver of the spatial patterning of PLK4 at the centriole and plays a critical role in selecting a single centriole duplication site
Professional Learning to Support Academic Librarians as Information Literacy Educators
No full textInformation literacy is a growing concern in higher education and academic libraries in the United States. Broadly defined, information literacy is the finding, understanding, and use of information (ACRL, 2015). Academic librarians are often the primary information literacy educators and proponents in higher education settings and are increasingly expected to integrate information literacy into libraries and higher education curricula. The Association for College and Research Libraries (ACRL) shifted the definition for information literacy from skills-based to concept-based in 2015. Librarians across higher education have struggled to make the change and embrace their roles as information literacy educators. Librarians in a small liberal arts college demonstrated specific needs inhibiting their ability to shift their practice: (a) they had not been systematically or intentionally trained in teaching information literacy, (b) they were unfamiliar with concept-based information literacy, and (c) they struggled to communicate both information literacy and their role as information literacy educators. Situated in sociocultural learning theory, the purpose of this study was to investigate how librarians at Sunview College experienced a professional learning program, specifically, a lesson study, and how their participation contributed to their knowledge of concept-based information literacy, teaching, and perceptions of their roles as educators. The study was designed as a qualitative case study using a holistic single-case design (Yin, 2018) to evaluate the outcomes and the process of the intervention. At the conclusion of the study, (a) librarians described information literacy as a set of concepts rather than a set of skills, (b) librarians incorporated information literacy concepts into their teaching, and (c) librarians described parts of their professional role as a contributor to student learning. However, the librarians struggled with defining information literacy, had specific preferences in information literacy teaching, and described their role as educators primarily embedded within a particular job role. Additionally, the librarians demonstrated evidence of one of the intermediate outcomes: increased confidence in using and discussing the ACRL Framework.
The findings suggest that lesson study may be an effective model for professional learning for librarians in learning about and teaching information literacy adaptable to other contexts
MODELING CONTRACTILITY KIT-MEDIATED MECHANORESPONSIVENESS AND CYTOSKELETAL NETWORK ASSEMBLY
No full textCell shape change processes rely on a dynamic network of macromolecules. The proper function of this network enables mechanosensation, the cell’s ability to sense and respond to mechanical cues. Myosin II and cortexillin I, critical elements of the cellular mechanosensory machinery, preassemble in the cytoplasm of Dictyostelium cells into complexes that we have termed contractility kits (CKs). Two IQGAP proteins then differentially regulate the mechanoresponsiveness of the cortexillin I-myosin II elements within CKs. This dissertation investigates the mechanism of CK self-assembly, provides insight into possible molecular means for IQGAP regulation, and elucidates their role in mediating mechanosensation at the cellular level. To achieve this, a series of models of CK self-assembly and incorporation into the cellular cytoskeleton to mediate mechanoresponsiveness were created. Firstly, I developed a coarse-grained excluded volume molecular model of CK self-assembly to gain insight into the types of CKs that form, their size, their composition distributions, and diffusion coefficients. The model is parameterized using experimentally measured parameters acquired through fluorescence cross-correlation spectroscopy and fluorescence correlation spectroscopy, which describe the interaction affinities and diffusion coefficients for individual molecular components, and which have also been validated via several orthogonal methods. Simulations of wild-type and null-mutant conditions implied that the temporal order of assembly of these kits is dominated by myosin II dimer formation and that IQGAP proteins mediate cluster growth. Our simulations also predicted the existence of “ambiguous” CKs that incorporate both classes of IQGAPs, and we confirmed this experimentally using fluorescence cross-correlation spectroscopy. This molecular model serves to describe the formation and composition of the CKs at the molecular level. Secondly, I developed a deterministic reaction-diffusion model to investigate how CKs incorporate into the existing cellular cytoskeleton to regulate the cell’s response to an applied mechanical stimulus. The model has been developed using parameters extracted from the molecular model of CK self-assembly described above, as well as previous models of myosin II bipolar thick filament formation published in the lab. The model successfully reproduced experimental myosin accumulation profiles from micropipette aspiration experiments performed in Dictyostelium, as well as predicted a myosin accumulation profile for an mhckC mutant
INVESTIGATING THE ROLE OF COPPER BIOAVAILABILITY IN YES-ASSOCIATED PROTEIN 1 ACTIVITY
No full textCopper is an essential micronutrient in virtually all cell types. Though copper is critical to the function of many different types of enzymes, it was not until recently that kinases were found to be regulated by binding copper. Thus far, only three such kinases have been found to exist. Based on this emerging phenomenon of kinases being regulated by copper binding, we wondered whether the Hippo pathway, which relies on kinases for its activity, might also be regulated by copper.
The Hippo pathway relies on a core kinase cassette consisting of the upstream kinase MST1/2 and the downstream kinase LATS1/2. The pathway regulates many biological processes, including tumorigenesis, organ size homeostasis, wound healing, and differentiation. It accomplishes these various functions by regulating the phosphorylation state and localization of a transcriptional coactivator called YAP. When the Hippo pathway is off, YAP translocates into the nucleus and promotes transcription of pro-proliferative and anti-apoptotic genes. When the Hippo pathway is active, however, LATS1/2 phosphorylates YAP, resulting in its cytoplasmic retention and subsequent degradation. To our knowledge, there are no reports in the literature addressing whether YAP or the Hippo pathway are regulated by cellular copper levels, a gap that we sought to address.
When we tested the effects of the copper chelator TTM on YAP localization in cells, we found that YAP nuclear localization significantly increased in cells treated with both TTM and a Hippo pathway stimulus. Furthermore, these conditions also led to a significant increase in YAP target gene transcription. When we examined the effects of TTM on the Hippo pathway, we were surprised to find that LATS1/2-mediated phosphorylation of YAP was unaffected by TTM treatment, suggesting that copper regulates YAP localization independently from the Hippo pathway. These results suggest that low cellular copper content can override the Hippo pathway, allowing phosphorylated YAP to translocate to the nucleus
Risk Factors for Seclusion in Children and Adolescents Inpatient Psychiatry: The Role of Demographic Characteristics, Clinical Severity, Life Experiences and Diagnoses
Get PDFEnhancing DataTrail Data Science Education: The BaltimoreTrails R Package and Shiny Web-App
Get PDFThis thesis presents BaltimoreTrails, a tool designed to enhance data science education within the DataTrail curriculum. By integrating Baltimore-specific datasets into an interactive Shiny Web-App, BaltimoreTrails provides unique data access and an interactive learning experience for students and educators.
Additionally, the tool aims to foster a deeper understanding of data science concepts through interactive data exploration and visualization, thereby enhancing the overall learning experience.
The development of this tool fills a knowledge gap by providing a software tool that enables the easy incorporation of many Baltimore-specific data sets into a graphical user interface to be used by students to support the teaching goals of the DataTrail program and adds directly to the curriculum by providing additional interactive tutorials and exercises on each DataTrail chapter
Searching for Success in Failure: A Case for "Strategic Trust" in U.S.-North Korean Nuclear Negotiations
No full textIn the absence of U.S. policy options that can counter the North Korean nuclear threat without risking war or approaches that can pressure the regime to surrender its strategic capabilities via sanctions or non-engagement, a re-examination of the negotiation option seems warranted. Given that nuclear negotiations, however, have repeatedly failed since the collapse of the 1994 Agreed Framework, identifying an underlying reason for the series of failures is critical if parties seek to understand possible levers of influence in future negotiations. Yet the lack of consensus within the academic community in identifying one primary reason for failure merited a review of U.S. and North Korean statements, which appeared to attribute responsibility to a perceived lack of trust. Literature, however, shows that trust is not a requirement for cooperation, and actors’ rational calculations of political interests and risks, in fact, serve as the key factor in leading parties to cooperate. As a result, cooperation results as part of a strategic decision to engage—or rather, through the existence of what is termed “strategic trust” in this thesis. The presence of strategic trust is determined by parties’ ability to demonstrate the following: 1) an understanding of the other sides’ interests and motivation to address them through a zone of possible agreement (ZOPA), 2) capacity to follow through on commitments, and 3) willingness to engage and commit to the process. Using qualitative analysis, the presence or absence of strategic trust is assessed in three examples of nuclear negotiations with North Korea: 1) the Agreed Framework process, 2) the Six Party Talks, and 3) the U.S.-North Korean summits. While parties’ creation of a ZOPA in 1994 led to a signed agreement, the insufficiency of this first strategic trust element alone in sustaining the process through the implementation phase without the presence of the remaining two strategic trust components contributed to the eventual collapse of the Agreed Framework. Findings further indicate that strategic trust was absent over a series of negotiations over time, hindering prospects for cooperation