Doctor of Philosophy

dissertationMelanoma is a malignant tumor that develops from melanocytes, which are pigmented cells primarily found in the epidermis, eye, and mucosal epithelia. Melanomas can occur in any tissue containing melanocytes. Although both cutaneous and uveal melanomas are derived from melanocytes, they have significant differences in terms of genetic alterations, metastatic pattern, tumorigenesis, and therapeutic response. In this dissertation, I present the results of studies that explore the role of the small GTPase ARF6 in cutaneous and uveal melanoma. These studies show that ARF6 is required both for invasion and metastasis in cutaneous melanoma and for orchestrating oncogenic G protein-mediated signaling pathways that promote uveal melanoma cell proliferation. In cutaneous melanoma cells, WNT5A-FZD4-LRP6 signaling activates ARF6 via the guanine nucleotide exchange factor (GEF) GEP100. ARF6 activation promotes the release of -catenin from cell-surface N-cadherin, thereby increasing the pool of cytoplasmic and nuclear -catenin with a subsequent induction of transcription, invasion, and metastasis. As WNT signaling is implicated in many cancers, these findings suggest that a WNT-ARFGEF-ARF signaling module may play an important role in the metastasis of multiple cancers. Uveal melanoma is the most common primary intraocular tumor. Activating mutations in GNAQ and GNA11, which encode members of the q class of the G-protein alpha subunit (Gq), are the primary drivers of uveal melanoma tumorigenesis. I show iv that oncogenic GNAQ forms a complex with GEP100 to activate ARF6, which in turn induces all known GNAQ-mediated signaling pathways as well as the relocalization of -catenin from the cell surface to the nucleus. These findings indicate that ARF6 is the primary immediate effector of an oncogenic GNAQ/GEP100 complex that regulates multiple signaling pathways shown to be important in the control of uveal melanoma tumorigenesis and growth. These results not only provide an improved understanding of the molecular mechanism underlying Gq-mediated tumorigenesis but also suggest a new target for therapeutic intervention in uveal melanoma

A Study of Non-computing Majors\u27 Growth Mindset, Self-efficacy and Perceived CS Relevance in CS1

As the demand for programming skills in today’s job market is rapidly increasing for disciplines outside of computing, CS courses have experienced spikes in enrollment for non-majors. Students in disciplines including art, design and biological sciences are now often required to take introductory CS courses. Previous research has shown the role of growth mindset, self-efficacy and relevance in student success within CS but such metrics are largely unknown for non-majors. In this thesis, we surveyed non-majors in CS1 at Cal Poly, San Luis Obispo during the early and late weeks of the quarter to gain insights on their growth mindset, their self-efficacy and the perceived relevance of the course to their lives. In our analysis, we discovered that non-majors’ levels of growth mindset and of self-efficacy decreased throughout the duration of CS1 with additional differences by gender. However, non-majors largely found that the material covered in CS1 was highly relevant to their academic and professional careers despite being challenged by it. These findings provide important insights into the experiences of non-majors learning to code and can help better serve a more diverse population of students

Usefulness of Contralateral Indirect Decompression through Minimally Invasive Unilateral Transforaminal Lumbar Interbody Fusion

Study DesignRetrospective study.PurposeThis study aims to investigate the clinical and radiological results of contralateral indirect decompression through minimally invasive unilateral transforaminal lumbar interbody fusion (MI-TLIF).Overview of LiteratureSeveral studies have proposed that blood loss and operation time could be reduced through a unilateral approach, although many surgeons have forecast that satisfactory foraminal decompression is difficult to achieve through a unilateral approach.MethodsThe study included 30 subjects who had undergone single-level MI-TLIF. Visual analogue scale (VAS) and Oswestry disability index (ODI) were analyzed for clinical assessment. Disc height, segmental lordosis, and lumbar lordosis angle were examined for radiological assessment. The degree of contralateral indirect decompression was evaluated through a comparative analysis, with a magnetic resonance imaging (MRI) performed preoperatively and at one year postoperatively.ResultsIntraoperative blood loss volume was 308.75 mL in the unilateral approach group (UAP), and 575.00 mL in the bilateral approach group (BAP), showing a statistically significant difference. Operation time was 139.50 minutes in the UAP group, and 189.00 minutes in the BAP group, exhibiting a statistically significant difference (p0.05).ConclusionsSatisfactory results were acquired with MI-TLIF conducted through the unilateral approach of contralateral indirect decompression, in alignment with the bilateral approach. Therefore, contralateral indirect decompression is thought to be a useful procedure in reducing the operation time and volume of blood loss

Effects of different creep feed types on pre-weaning and post-weaning performance and gut development

Objective This experiment was carried out to determine the effects of different creep feed types on suckling performance and further adjustments to solid feed after weaning. Methods A total of 24 multiparous sows and their litters were allotted to one of three treatment groups: i) provided highly digestible creep feed (Creep), ii) provided a pig weaning diet (Weaner), and iii) provided sow feed (Sow) as creep feed until weaning. After weaning, a total of 96 piglets were selected for evaluation of post-weaning performance. Results For pre-weaning performance, the Creep treatment led to a significantly higher feed intake from 14 to 28 d (p<0.05) and higher body weight gain from 21 to 28 d than piglets that were provided other diets. However, after weaning, the Weaner treatment yielded a significantly higher feed intake and average daily gain than other treatments from 0 to 14 d after weaning (p<0.05); Creep treatment tended to generate lower villus heights in the duodenum than the other treatments (p = 0.07). Conclusion Highly digestible creep feed improved pre-weaning performance, but feed familiarity and grain-based creep feed improved post-weaning performance

Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel

Connexin family proteins assemble into hexameric channels called hemichannels/connexons, which function as transmembrane channels or dock together to form gap junction intercellular channels (GJIChs). We determined the cryo-electron microscopy structures of human connexin 31.3 (Cx31.3)/GJC3 hemichannels in the presence and absence of calcium ions and with a hearing-loss mutation R15G at 2.3-, 2.5-, and 2.6-A resolutions, respectively. Compared with available structures of GJICh in open conformation, Cx31.3 hemichannel shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion-binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. We also found that the hemichannel has a pore with a diameter of ~8 A and selectively transports chloride ions. Our study provides structural insights into the permeant selectivity of Cx31.3 hemichannel

Stochastic Particle Flow for Nonlinear High-Dimensional Filtering Problems

A series of novel filters for probabilistic inference that propose an alternative way of performing Bayesian updates, called particle flow filters, have been attracting recent interest. These filters provide approximate solutions to nonlinear filtering problems. They do so by defining a continuum of densities between the prior probability density and the posterior, i.e. the filtering density. Building on these methods' successes, we propose a novel filter. The new filter aims to address the shortcomings of sequential Monte Carlo methods when applied to important nonlinear high-dimensional filtering problems. The novel filter uses equally weighted samples, each of which is associated with a local solution of the Fokker-Planck equation. This hybrid of Monte Carlo and local parametric approximation gives rise to a global approximation of the filtering density of interest. We show that, when compared with state-of-the-art methods, the Gaussian-mixture implementation of the new filtering technique, which we call Stochastic Particle Flow, has utility in the context of benchmark nonlinear high-dimensional filtering problems. In addition, we extend the original particle flow filters for tackling multi-target multi-sensor tracking problems to enable a comparison with the new filter

Quality Assessment of Randomized Controlled Trials Published in the Korean Journal of Urology Over the Past 20 Years

PURPOSE: Because low-quality trials may lead to erroneous conclusions, quality assessments are necessary. Thus, in this study, we scrutinized randomized controlled trials (RCTs) published in the Korean Journal of Urology (KJU) to assess their quantity and quality. 0aMATERIALS AND METHODS: Upon extracting RCTs from all articles published in the KJU from 1991 to 2010, assessments were made on the basis of the Jadad scale and the adequacy of allocation concealment. The selections and assessments were performed independently by two researchers, and adjustment of the differences was done by a third-party researcher. In addition, the factors that may affect quality were analyzed. 0aRESULTS: A total of 3,516 original articles were searched and 28 RCTs were extracted. In the 1990s, RCTs constituted only 0.27% of the total original articles, but in the 2000s, RCTs constituted 1.34%. The mean total Jadad score increased from 1.6 points in the 1990s to 1.65 points in the 2000s. However, the percentage of &quot;good quality&quot; trials also increased from 20% to 30.43%. As for adequate allocation concealment, one study was observed in the 2000s. The aspect most lacking was appropriate dropout and double-blinding. Studies with medical interventions or funded or examined by institutional review boards tended to receive higher quality assessments. 0aCONCLUSIONS: Although RCTs consistently increased in both quantity and quality, in future studies, researchers should continue to strive toward achieving adequate allocation concealment and appropriate double-blinding. In addition, researchers must become more interested in receiving external funding and undergoing examination by institutional review boards