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L2 Acquisition of Korean Obstruents by Mandarin Speakers: The Relationship between Perception and Production
Get PDFThe study investigates the relationship between perception and production in the second language acquisition of Korean obstruents by native Mandarin speakers. Drawing on the Speech Learning Model (SLM) and the revised framework (SLM-r), this thesis explores how learners perceive and produce Korean’s three-way contrast: lenis, fortis, and aspirated stops and affricates, and whether perceptual sensitivity predicts production accuracy. Thirteen Mandarin-speaking Korean learners participated in both production and discrimination perception experiments. Acoustic analyses focused on VOT and F0, the primary cues distinguishing Korean obstruents.The results indicate that Mandarin-speaking learners heavily rely on VOT in both perception and production, reflecting L1 transfer. As native speakers of a tonal language, they are not sensitive to F0, which plays a critical role in Korean phonology. Production and perception are not aligned in all consonantal contrasts and do not consistently correlate. Some learners exhibit accurate production despite poor perception and vice versa. These findings support part of the claims of the SLM while challenging the assumption of a straightforward perception and production link in SLM-r. The study suggests that targeted instruction on F0 may be necessary to enhance learners’ acquisition accuracy in Korean. Future research should examine how instructional context and explicit tonal training influence the acquisition of F0 cues for consonant laryngeal contrasts in L2 Korean.Master of Art
EXPLORATION OF NOVEL C-H FUNCTIONALIZATION METHODOLOGIES VIA ORGANIC PHOTOREDOX CATALYSIS
Get PDFThe selective and facile functionalization of C-H bonds – the most abundant bonds in all chemical space – remains a key driving factor for innovation in modern chemistry. Chapter 1 provides an overview of C-H functionalization research and its importance; discussion of C-H functionalization necessitates an analysis of subjects such as organometallic chemistry, radical generation and functionalization, and the synthetic benefits and challenges presented therein. Intersecting with discussion of C-H functionalization and radical chemistry, photoredox catalysis has played a major role in modern C-H functionalization methodologies, and as such is discussed in detail. Distinct and impactful C-H functionalization works from the Nicewicz lab are explored, providing a basis for the exploratory photoredox catalysis chemistry discussed in subsequent chapters.Chapter 2 explores attempts at generating and functionalizing azaallyl radical species via organic photoredox catalysis. Using the extreme oxidizing power of acridinium photoredox catalysts for novel modes of C-H functionalization circumvents the typically harsh conditions needed for azaallyl radical formation. While methods for α-amino functionalization are abundant, azaallyl radicals are uniquely long-lived, allowing for radical cascade and cyclization reactivity. While some success was afforded C-H functionalization with typical radical traps, control of the reactivity remains tenuous and the desired cascade-like cyclization remains elusive. Chapter 3 details a completed C-H functionalization methodology for the programmable synthesis of decorated piperazine cores via organic photoredox catalysis. The synthetic and medicinal importance piperazines is highlighted, as are the typical shortcomings of both traditional and state-of-the-art approaches for their synthesis. Optimization and scope of the cyclization reaction are explored in depth, and a complementary hydroamination strategy for the synthesis of complex diamine backbones from ene-carbamates via organic photoredox catalysis is demonstrated. Chapter 4 serves as a conceptual successor to the piperazine methodology, establishing the foundation of a synthetic approach for an organic photoredox-catalyzed morpholine synthesis via a C-H functionalization strategy. Initial optimization of the desired reactivity is detailed in full, exploring somewhat divergent results based on seemingly innocuous changes to the reaction system. While the yield in either iteration of the model system remains low, significant options for future optimization remain in terms of catalyst choice and substrate design.Doctor of Philosoph
IMPACT OF CLIMATE FACTORS ON PEDIATRIC ENTERIC INFECTIONS IN MAPUTO, MOZAMBIQUE
Get PDFDiarrheal diseases are common in low- and middle-income countries, and climate can influence how enteric pathogens spread in underserved communities. We examined pathogens in stool samples – as a proxy indicator of enteric infection – as part of a cross-sectional follow-up of children in the Maputo Sanitation trial. Using Poisson regression models, we estimated prevalence ratios to determine how precipitation and temperature were associated with pathogen presence and performed an additional analysis comparing the impact of control and intervention compounds on this relationship. We found that most bacteria were associated with higher temperatures. Viruses and protozoa were observed to be more common during drier conditions. The additional analysis found differential effects: high precipitation preceding sampling was associated with higher detection of pathogens in control compounds; elevated temperatures were associated with intervention compounds. Further research on the specific associations between sanitary infrastructure, climate, health, and additional climate variables is warranted.Master of Scienc
Synergistic co-targeting of KRAS and MYC in KRAS-dependent cancer using ligand-directed inverted chimeric RNAi molecules
Get PDFActivating mutations in the GTPase KRAS are responsible for driving nearly 25% of all cancer types. Despite extensive research, effective KRAS inhibitors remained elusive until recently. The discovery of covalent molecules that irreversibly bind to the KRASG12C mutant protein, present in approximately 15% of cancer patients, facilitated the development of KRASG12C-specific inhibitors. However, clinical evidence of rapidly acquired resistance to KRASG12C inhibitors underscores the need for therapies that can overcome these challenges and target non-KRASG12C mutations. Mutant KRAS cooperates with the transcription factor MYC to promote tumorigenesis, and dual targeting of KRAS and MYC has shown synergistic anti-cancer effects in murine models. We have developed highly potent siRNAs against KRAS and MYC that inhibit downstream signaling and key cancer phenotypes. Using an endo-nucleolytic DNA bridge, we created an RNAi molecule that link MYC- and KRAS-targeting siRNAs in “serial” and “inverted” chimeric conformations. Compared to both serial chimeras and individual siRNAs, the inverted chimeric siRNA designs achieved superior gene silencing, resulting in ~40-fold reduction in cell viability and loss of tumorigenic potential. Mechanistic studies reveal that endosomal cleavage of the chimeric siRNA generates 2’-deoxythymidine (dT) 5’-terminal overhangs on the antisense strand, further enhancing target silencing in a dose-dependent manner. This chimeric siRNA design establishes proof-of-concept for dual KRAS and MYC silencing and represents a new molecular strategy for co-targeting any two genes of interest with broad implications.Doctor of Philosoph
Nonoccupational Physical Activity During Pregnancy, Behavioral Risk Factor Surveillance System, United States, 2023.
Get PDFPhysical activity during pregnancy has numerous health benefits. This cross-sectional study examined the prevalence of nonoccupational physical activity among pregnant women aged 18 to 49 years in the United States. Using 2023 Behavioral Risk Factor Surveillance System data, we estimated the prevalence of meeting the aerobic guideline (≥150 minutes/week of moderate intensity-equivalent aerobic activity) and muscle-strengthening activity (≥2 episodes/week) among 2104 pregnant women aged 18 to 49 years in the United States and explored sociodemographic differences with adjusted logistic regression modeling. Overall, 49.0% (44.5%-53.4%) and 28.6% (24.9%-32.2%) of women met the aerobic activity guideline and participated in ≥2 episodes per week of muscle-strengthening activity, respectively. In adjusted analyses, we found sociodemographic differences for meeting the aerobic activity guideline (by age, race and ethnicity, and general health) and for participating in ≥2 episodes per week of muscle-strengthening activity (by general health). Opportunities exist to increase physical activity among pregnant women of diverse backgrounds through comprehensive, multilevel approaches so that more people can experience its health benefits
Acceptance and Adoption of Artificial Intelligence Among Cancer Survivors Seeking Information: A Literature Review
Get PDFWith artificial intelligence (AI) on the rise in healthcare, we investigated the acceptance and adoption of AI among cancer survivors who are seeking information. We searched 3 databases—PubMed, Scopus, and CINAHL for original research studies examining cancer survivors’ acceptance and adoption of AI while seeking information. We screened 858 articles, resulting in the inclusion of 12 studies. Cancer survivors’ perceived benefits of AI include diagnostic accuracy, improved healthcare access, and reduced healthcare costs. Concerns included the loss of human interaction, data loss, and privacy issues. Adoption and acceptance of AI-based Chatbots and cancer trial search tools were also demonstrated. Regarding the ethical use of AI, cancer survivors shared a desire for data de-identification, disclosure, and transparency. Cancer survivors accepted AI as an adjunct to physicians. Patients demonstrated acceptance and adoption of both AI-based educational tools and search engines. Developing AI models with better explainability and education can improve cancer survivors’ acceptance and adoption of AI
Editorial: Building tomorrow's biomedical workforce: advancing scholarship, innovation and systemic change
Get PDFSustaining innovation and excellence in the U.S. biomedical research enterprise depends on cultivating a skilled workforce prepared to address future challenges and excel across a growing array of professional roles. Today’s biomedical scientists face a variety of challenges across the career trajectory, including limited exposure to the full breadth of career paths, extended training timelines, heightened uncertainty around career prospects, hypercompetition, the growing instability of research funding, and exclusion of scientists from historically underrepresented groups. These issues are compounded by structural systems that under-acknowledge contributions to team science, innovation, and mentoring, relative to metrics like publications and grants (Alberts et al., 2014; Pickett et al., 2015; National Academy of Sciences, Engineering, and Medicine, 2014, 2018; National Academies of Sciences, Engineering, and Medicine, 2019; Council of Graduate Schools, 2025; Okahana, 2019). Addressing these challenges is essential to maintaining U.S. competitiveness and creating pathways that attract, retain, and prepare a highly talented and diverse pool of scientists contributing to the STEM workforce and broader economy (National Institutes of Health, 2012). Our Research Topic, Building Tomorrow’s Biomedical Workforce: Evaluation of How Evidence-Based Training Programs Align Skill Development and Career Awareness with a Broad Array of Professions, tackles these and other challenges, in order to develop the researchers of tomorrow
Quantifying hydrothermal ammonium mobilization from sediment and implications for the marine biosphere: a case study from the Guaymas Basin, Gulf of California
Get PDFFluid-rock interactions in hydrothermal systems are capable of liberating ammonium (NH4+) from sedimentary organic material and making it bioavailable for benthic and pelagic microbial communities. Hydrothermal systems in organic-rich sedimentary basins are therefore thought to have played a key role in supplying bioavailable nitrogen to the early biosphere. To place new quantitative bounds on this process, we examined sediments from active hydrothermal systems in the Guaymas Basin, a young oceanic spreading center in the Gulf of California. We analysed four shallow sediment cores that were taken in the Guaymas Basin’s hydrothermally-active Southern Trough. We used a combination of isotopic tracers (δ15N, δ13C) and elemental abundances to explore nitrogen and metal mobility in buried sediments. We found that ca. 54% of the organically-bound nitrogen is remobilized by active seepage in the top 10 cm of the sediment package within as little as 27–83 yr. Extrapolating these findings over the hydrothermally-active area of the basin yields an ammonium seepage flux of ca. 1.3–4.1 mol/s. In addition, high temperature venting liberates ca. 156–187 mol/s, as estimated from previous data. Assuming biological uptake of hydrothermally recycled ammonium in the water column, these fluxes could support up to 1.3% and 58% of export productivity, respectively. Our data also reveal that the accumulation of micronutrients or potentially toxic metals is influenced by the presence of organic material in seep sediments. The Guaymas case study demonstrates that hydrothermal seepage in sedimentary basins can create a significant nutrient flux and is an efficient means of recycling nutrients from organic matter at shallow burial depths. Hydrothermal nutrient fluxes could therefore have enhanced microbial activity in Earth’s history, in particular during time intervals when Earth’s oceans are thought to have been nutrient-depleted. Our data also highlight the role of organic material in enhancing metal mobilization and accumulation in otherwise metal-starved hydrothermal seeps
Statistical and Analytical Innovations For High-Resolution Paleoclimate Reconstructions Using Corals and Bivalves
Get PDFHigh-resolution marine archives (e.g., corals and bivalves) offer critical insight into past climate variability. However, many potential archives are either inaccessible due to slow growth rates, or limited in interpretability due to non-climate-related variability in their skeletal geochemistry. This dissertation seeks to advance both analytical and statistical techniques to improve the fidelity, resolution, and reproducibility of paleoclimate reconstructions from two key high-resolution marine archives: the high latitude bivalve Astarte borealis and tropical Porites corals. Chapter 2 explores the use of secondary ion mass spectrometry (SIMS) to generate ultra-high-resolution δ18O records from A. borealis collected in the southern Baltic Sea. These records are used to assess the sensitivity of shell δ18O values to local and regional environmental variability, demonstrating strong correlations with salinity, temperature, and large-scale climate modes such as the North Atlantic Oscillation. The results establish A. borealis as a viable high-latitude proxy archive capable of recording hydroclimatic variability over seasonal to decadal scales. Chapter 3 introduces a novel analytical framework for converting two-dimensional LA-ICP-MS maps from Porites astreoides into one-dimensional time series, enabling high-resolution reconstructions of sea surface temperature (SST) and seawater pH. This chapter also presents the Scleractinian Multivariate Isotope and Trace Element (SMITE) method, a multivariate calibration method that leverages geochemical covariance to improve reconstruction skill. SMITE is shown to outperform traditional univariate methods in terms of accuracy, robustness to noise, and reproducibility across synthetic experiments and short coral datasets. Chapter 4 evaluates the performance and reproducibility of SMITE, Sr/Ca, and Li/Mg temperature estimates using 15 coral records from the Great Barrier Reef and 2 records from the Galápagos Archipelago. Synthetic climate field reconstructions reveal tradeoffs between statistical performance and signal recoverability, with SMITE providing more reproducible calibrations at the expense of variance suppression. Together, these chapters demonstrate a flexible and scalable approach for enhancing both analytical access and statistical rigor in high-resolution marine paleoclimatology. By extending proxy coverage into high-latitude environments and establishing a multivariate statistical framework for tropical coral reconstructions, this work lays the foundation for next-generation paleoclimate proxy networks and climate data assimilation efforts.Doctor of Philosoph
ESTRADIOL’S EFFECT ON REWARD-RELATED FUNCTIONAL CONNECTIVITY IN PERIMENOPAUSE-ONSET MAJOR DEPRESSIVE DISORDER
Get PDFHormone replacement therapy with estradiol (E2) alleviates mood symptoms in perimenopausal major depressive disorder (PO-MDD), but its neural mechanisms remain unclear. This study examined frontostriatal connectivity changes during reward processing in 15 PO-MDD and 16 control participants who completed pre- and post-treatment fMRI scans following three weeks of transdermal E2. Before treatment, PO-MDD participants showed reduced frontostriatal connectivity during reward anticipation and receipt. Group × time analyses revealed increased connectivity over time in PO-MDD participants from regions including the caudate, putamen, insula, and amygdala, whereas controls showed the opposite pattern. Connectivity changes from the amygdala, DLPFC, and insula during reward anticipation and receipt predicted symptom trajectories: increased connectivity between some regions (e.g., amygdala–thalamus) and decreased in others (e.g., DLPFC–middle frontal gyrus) were linked to greater reductions in dysphoria and anhedonia. Findings suggest that E2-related symptom improvement in PO-MDD may involve restoration of reward circuitry connectivity, particularly during reward anticipation.Master of Art