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Oligodendrocyte Degeneration and Regeneration Dynamics in the Mouse Cerebral Cortex
No full textMyelin patterns in cortical gray matter are highly variable between cell types and along individual axons, with many exhibiting discontinuous myelination. Once formed, myelin sheaths are very stable, suggesting that these variable myelination patterns are functionally relevant. Indeed, loss of oligodendrocytes and myelin alters neuronal activity and is associated with physical and cognitive deficits in multiple sclerosis (MS). Although some myelin can be restored after a demyelinating injury and in diseases such as relapsing-remitting MS, previous studies showed that remyelination following cuprizone-induced demyelination leads to novel myelination patterns in somatosensory cortex, with oligodendrocytes regenerating in novel locations, and that the potential to regenerate the number of lost oligodendrocytes decreases with cortical depth, leading to an inefficient recovery. However, whether these dynamics are specific to somatosensory cortex or the cuprizone demyelination model remains unknown.
By leveraging two-photon in vivo imaging in transgenic mice, I show that oligodendrocytes in visual cortex are more resistant to cuprizone-mediated cell death than in somatosensory cortex, whereas the cortical depth-dependent potential to recover was comparable across cortical regions. Oligodendrocytes in visual cortex also regenerated in novel locations, suggesting that remyelination remodels cortical myelination patterns. In addition, we generated and characterized an inducible cell-specific Cre-dependent genetic ablation model to reduce potential off-target effects of chemical demyelination methods. This diphtheria toxin (DT)-mediated demyelination model also exhibited a decrease in oligodendrogenesis potential in deeper layers of the somatosensory cortex. We also found a striking oligodendrocyte degeneration profile in which DT-mediated apoptosis leads to demyelination in two discrete waves, regardless of animal age, with extensive degeneration occurring between five to seven weeks after baseline. Finally, we show that recently generated oligodendrocytes are more vulnerable to degeneration and that myelin decompaction is minimal prior to sheath degeneration and subsequent soma degeneration during cuprizone exposure and characterized the progressive chromatin compaction across the oligodendrocyte lineage. Together, this study reveals a variable susceptibility of oligodendrocytes based on cell age, cortical regions, and demyelination models and the striking limitation of oligodendrocyte precursor cells (OPCs) to generate a complete regenerative response, while providing a new experimental platform to longitudinally study oligodendrocyte dynamics in vivo
Topics in p-adic analysis
No full textSince their introduction by Hensel more than 100 years ago, the p-adic numbers have been playing a fundamental role in mathematics, number theory in particular, and nowadays it is hardly an exaggeration to contend that they are no less important than real and complex counterparts, due to its wide range of connections with other branches like rigid analytic geometry, p-adic Hodge theory, Iwasawa theory, and so on. In this dissertation, we present a total of 3 topics that crucially employ ideas and techniques from p-adic analysis. More precisely, these topics are:
- Sum expressions for totally real p-adic L-functions: In Chapter 2 and 3, we establish the infinite sum expressions of totally real p-adic L-functions, generalizing the earlier works of Delbourgo. This uses crucially the computational tool provided by the Amice-Mazur p-adic Fourier transform. As applications, we present a generalization of the Ferrero-Greenberg formula in the totally real setting, as well as a numerical criterion of the vanishing of the mu-invariant à la Iwasawa--Ferrero.
- On the BDP Iwasawa main conjecture for modular forms: Under the Heegner hypothesis, Kobayashi--Ota showed that one inclusion of the Iwasawa main conjecture involving the Bertolini--Darmon--Prasanna p-adic L-function holds after tensoring by Q_p. In Chapter 4, under certain hypotheses, we present the joint work with Antonio Lei, in which we show that the same inclusion holds integrally. This uses several modern developments in p-adic analysis, including Perrin-Riou's exponential/logarithm map, Pollack-Sprung's factorization into Coleman maps and its formulation in terms of p-adic Hodge theory by Lei and collaborators.
- Note on p-adic local functional equation: Given distinct primes l, p, in the first part of Chapter 5 we record a p-adic valued Fourier theory on a local field K over Q_l, which is developed under the perspective of group schemes. The second part studies the Haar measure of K and befitting Schwartz class functions, and their zeta integrals in a rigid analytic setting. Eventually, following Tate’s original argument, it proves a p-adic local functional equation over K that uncannily resembles the complex one found in Tate thesis
BEST PRACTICES FOR PROMOTING DIVERSITY, EQUITY, AND INCLUSION IN RESEARCH STUDIES: A STUDY OF THE ROLE OF RESEARCH ADMINISTRATORS
No full textThis capstone project identifies best practices for promoting diversity, equity, and inclusion in the recruitment and retention of research administration personnel. The qualitative research conducted within this project encourages a greater level of effort to be made in enhancing the amount of diversity in the field of RA via the publication of these findings. The recommended best practices were derived from RA professionals at higher education institutions in the U.S. whose thoughts were collected through questionnaires and interview activities. The key findings indicate that many of the recommended DEI initiatives possess low implementation costs and are not difficult to establish. However, some initiatives, such as programmatic actions, may require significant financial investment, particularly for smaller institutions. The project ultimately suggests that a balance of program-based actions and behavioral modifications has the potential to effectively increase the recruitment and retention rates of diverse RA personnel in HEIs. Further studies are required to corroborate these findings
Visualizing brain size evolution in platyrrhine monkeys: a skull reconstruction, endocast extrapolation, and volume comparison of Cebupithecia sarmientoi
No full textIn 2018, at the paleontological site La Venta, Colombia, the first complete monkey skull from the Middle Miocene epoch (11-13 MYA) was recovered. Paleontologists identified the skull as Cebupithecia sarmientoi, an extinct species of platyrrhine monkey whose skull was only previously known by teeth and mandible fragments. C. sarmientoi is most likely related to the Pitheciidae family of platyrrhine monkeys but has a noticeably smaller cranial cavity. This discrepancy indicates that C. sarmientoi had a smaller brain size than its extant relatives. To confirm the relative brain size, a digital 3D model of the fossil was reconstructed and a cast of the cranial cavity, or endocast, was created. The volume of the endocast was compared to 16 closely related living species of platyrrhine monkey using an RMA regression and the relative brain sizes were placed in evolutionary trees. This is the first study to attempt to extrapolate an endocast after a skull reconstruction and the workflow was assessed for future research. These visualizations of C. sarmientoi are the first of their kind and provide new insights on the rate and timing of brain size increase in platyrrhine monkey evolution. The visualizations will contribute to scientific publications on the C. sarmientoi discovery and enhance public understanding and interest in evolution and paleontology
Aligning Classroom Expectations to Individual Student Needs: A Professional Development Intervention to Improve Teachers’ Data Literacy
No full textStudents with significant cognitive disabilities often have complex needs, requiring teachers to be equipped with the knowledge and tools necessary to provide appropriately aligned instruction. Through the lens of sociocultural theory, as well as the theory of improvement science, this study aimed to build the capacity of teachers to implement effective data literacy skills in an effort to align appropriate classroom expectations to students with significant cognitive disabilities. Exploration of needs assessment data revealed the need for ongoing collaboration and communication, as well as supports in the learning environment, including adequate teacher preparation to effectively plan instruction and appropriately document and report on student progress. The results of the intervention, a mixed methods case study, revealed teachers had more positive perceptions of their data literacy skills when provided a structured data monitoring framework that helped to focus on smaller increments of change in student performance. In addition, participants reported a positive influence on their self-efficacy and attitudes towards data use, when provided collaborative support from a knowledgeable coach, including ongoing opportunities for feedback and reflection. Moving forward, it is important to continue implementing research studies that specifically focus on this unique population of learners with significant cognitive disabilities
EXPLORING GENETIC COUNSELORS’ USE OF TUMOR SEQUENCING TO IDENTIFY GERMLINE VARIANTS: TIME FOR A CHANGE IN SCOPE?
No full textObjective: Tumor sequencing (TS) is used by most oncologists for precision treatment 1-4, and has now been found to reveal potential germline cancer predisposition variants (PGCVs) in ~12-14% of cases 5-7. Reviewing TS results to identify PGCVs requires expertise, though guidelines have not yet established different clinicians’ responsibilities in result interpretation and making necessary referrals 8-10. When PGCVs are identified, referral to cancer genetic counselors (GCs) for confirmatory germline testing and risk assessment is recommended 8-10. Cancer GCs are a good fit for both identifying PGCVs and referral for confirmatory testing, though cancer GCs current role and attitudes related to this work are unknown. This study targeted cancer GCs to describe the current state of the field and possibly inform future management.
Methods: An anonymous, online, descriptive survey of closed and open-ended questions was sent to cancer GCs in North America.
Results: Of 154 responses, 135 could be used in analysis. A majority (n = 128) had training on this topic, mostly through conferences (74.2%) or self-study (67.4%). Clinical workflows were listed as a top referral facilitator for these cases by most participants (n = 101, 86.3%), though for half this was not in place at their institution (n = 68, 50.4%). Over 90% endorsed TS PGCV identification and management as part of cancer GC scope of practice (n = 123-126). This work was also seen as part of scope of practice by over 90% for pathologists (n = 126), lab GCs (n = 127), and oncologists (n = 122). Family still appeared to be an important information for GCs recommend cancer risk assessment for case vignettes. Overall, responses to the vignettes and case study varied by practice setting, role of GC involvement, and training type. A majority used variant allele frequency, founder mutation status, and tumor type as PGCV clues.
Conclusions: While most respondents agreed that evaluating TS for PGCVs falls under cancer GC scope of practice, there were variations in individual roles, views on the scope of others, and interpretation and management strategies
TILLING FERTILE SOIL: USING HYBRID PROFESSIONAL LEARNING COMMUNITIES TO SUPPORT COLLEGE READINESS FOR URBAN HIGH SCHOOL STUDENTS
No full textUrban high schools provide consistent pipelines for minority serving institutions such as historically Black colleges and universities (HBCUs). Unfortunately, the number of urban high school graduates who require additional support, including remediation, to succeed in higher education has increased over the last decade. The challenges in supporting urban high school students have resulted in an equity gap in the high school graduation rates and college readiness of urban students compared to other high school students. This research explores factors contributing to the academic, social, and behavioral preparation of urban high school students pursuing postsecondary educational opportunities without the need for remediation. The research also examines the effects of teachers on college preparation beyond mastery of academic concepts and presents the framework for a professional learning community that supports community building for secondary and post-secondary educators with the goal of improving student learning outcomes
Identifiability and data-adaptive RKHS Tikhonov regularization in nonparametric learning problems
No full textWe provide an identifiability analysis for the learning problems (1) nonparametric learning of kernels in operators and (2) unsupervised learning of observation functions in state space models (SSMs). We show that in either case the function space of identifiability (FSOI) from the quadratic loss functional is the closure of a system-intrinsic data-adaptive reproducing kernel Hilbert space (SIDA-RKHS). We introduce a new method, the Data-Adaptive RKHS Tikhonov Regularization method (DARTR). The regularized estimator is robust to noise and converges as data refines. The effectiveness of DARTR is demonstrated through the following problems (1) nonparametric learning of kernels in linear/nonlinear/nonlocal operators and (2) homogenization of wave propagation in meta-material. We introduce a nonparametric generalized moment method to estimate non-invertible observation functions in nonlinear SSMs. Numerical results shows that the first two moments and temporal correlations, along with upper and lower bounds, can identify functions ranging from piecewise polynomials to smooth functions. The limitations, such as non-identifiability due to symmetry and stationary, are also discussed
Building an International Regulatory Regime in Submarine Cables and Global Marine Communications
No full textAbout 95 percent of worldwide Internet traffic travels from one continent to another through submarine communication cables working around the clock, while only the remaining 5 percent relies on satellite for communication (Coffey 2014, 28; van Ouderaren 2021). Thus, what seems to keep military officers and national security strategists in many states awake at night is the possibility that some military submarines have the capability of cutting submarine communication cables. For example, it is known that a Chinese submarine, Jiaolong, has such capability (Kim 2012, 68) as well as a Russian submarine Yantar (Fuller 2021).
A concern here is that in international waters there are not effective laws to hold the attacker responsible when the submarine cables are physically damaged as a result of physical attack by a state.
The purpose of this study is to find out which international legal regime applies to submarine communication cables and global marine communications. It also suggests some modifications for improving the current international legal system so that sensitive information, such as our email exchanges and health records, and the cables that carry this information can be better protected. To explore these questions, I have chosen to employ a historical approach, case studies, and insights from experts to inform my study.
In this dissertation, I apply the theory of international cooperative regime-building to the submarine communication cable industry and emphasize the South Korean government’s potential role as a catalyst in developing new norms. As one of the leading suppliers of fiber optic cables (Kim 2020), South Korea can play a crucial role in developing an international regime--and identifying the challenges to the current regulatory regime for submarine communication cables.
During this process, I intend to test a hypothesis that submarine cables are not being adequately regulated under the current international legal regime. Where I identify gaps in international law currently protecting submarine cables, I also offer policy recommendations to improve the regulatory regime, such as the idea of granting the right to punish an attacker under the cable owner’s jurisdiction rather than that of the attacker’s jurisdiction when the cable is laid in high seas—the position that UNCLOS currently takes according to Article 113