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IGF1 Establishes the Regulatory Stem Cell Niche of Human iPSC-Derived Forebrain Neural Stem Cells
No full textiPSC is a widely-used model for biomedical research. We developed a method of differentiating iPSC to form neural progenitor cells with forebrain cortical identity. Analysis of the neural progenitor cell showed that the IGF pathway is highly activated in the cell. Using molecular biology methods, we trace the origin of the IGF and role of IGF in the neural progenitor cells. We find that while the IGF receptor is expressed on the neural progenitor cell surface, the origin of IGF is exogenous, expressed by the HNF3β+ cell. The IGF regulated the forebrain cortical identity neural progenitor cell through the stem cell niche. IGF activates neural progenitor cell proliferation through increasing cells in G1/S1 phase, and does not affect cell apoptosis. Furthermore, we determined the downstream pathway of the IGF mitogenic effect, and found that the IGF regulates the cell through the PI-3K/AKT and mTORC pathway
Trends in Noninsulin Antidiabetic Medications in Patients with HIV and Type 2 Diabetes in North America, 2013 to 2021
Get PDFBackground: People living with HIV (PWH) have increased risks for type 2 diabetes (T2DM) and cardiovascular events (CVE). The use of novel noninsulin antidiabetic medications with cardiovascular benefits has been increasing over the past decade in general population. We described the utilization of noninsulin antidiabetic medications among PWH with T2DM using data extracted from electronic health records (EHR) from 2013 to 2021. To compare the methods measuring the utilization of medications, we reported the trends in prescriptions and applied assumptions to classify an individual’s regimen use.
Methods: Data of 19,565 eligible patients between April 1st, 2013 and December 31st, 2021 were derived from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Noninsulin antidiabetic medication use was measured based on annual number of prescriptions. Noninsulin antidiabetic regimen use was measured applying assumptions of the length of use from a single prescription. We used descriptive statistics to estimate the medication- or regimen-specific numbers and proportions for each calendar year, and Poisson regression with robust variance with generalized estimating equations to analyze the annual trends within the study period.
Results: The prescriptions of biguanide and sulfonylurea decreased from 2013 (58% and 30% of total prescriptions) to 2021 (45% and 13% of total prescriptions; p-trend < 0.001 and p-trend < 0.01, respectively). The prescriptions of glucagon-like peptide 1 agonists (GLP-1 RA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) increased from 2013 (1% and 0% of total prescriptions) to 2021 (19% and 12%; p-trend = 0.84 and p-trend = 0.93, respectively). Similar trends of regimen were seen with the application of different approaches for regimen classification. The difference in annual proportions of use between prescriptions and regimens was small (< 5 percentage point) except for sulfonylurea prescription and sulfonylurea monotherapy.
Conclusions: There was a rapid increase in the use of GLP-1 RA and SGLT2i among PHW with T2DM since the first approval of SGLT2i (2013) using prescription data from the EHR. Continued monitoring of the use of these medications and the impacts on CVE is needed
Exploring Vagueness and Ambiguity in Humans and Models Through Visual Question Answering
Get PDFThis thesis studies the impact of vagueness and ambiguity in visual question answering (VQA) on language understanding and computational models, offering insights important for advancing the field of computational linguistics and natural language processing.
In Chapter 1, I discuss the fundamental role of questions in bridging knowledge gaps and facilitating communication, emphasizing the inherent vagueness and ambiguity present in natural language questions. I emphasize the necessity of resolving ambiguous and vague questions for effective communication and information collection.
In Chapter 2, I review a previous project in which I explore vagueness through linguistic and computational methodologies within the Visual Question Answering and GQA datasets. By examining vague predicates and their implications, I investigate discrepancies between human and model responses, highlighting the nuanced challenges overlooked by traditional performance metrics. This effort, in collaboration with Elias Stengel-Eskin, resulted in the paper "Human-Model Divergence in the Handling of Vagueness''. I was responsible for data collection, cleaning, processing, and annotator management. The remainder was a collaboration with my coauthors.
In Chapter 3, I review a previous effort in which, focusing on lexical ambiguity, a subset of semantic ambiguity, I analyze a dataset of ambiguous examples and review a model designed from this dataset to generate questions that mitigate ambiguity and align with human interpretation. This effort, in collaboration with Elias Stengel-Eskin and Yi Zhou, resulted in the paper "Why Did the Chicken Cross the Road? Rephrasing and Analyzing Ambiguous Questions in VQA''. I was responsible for data collection, cleaning, processing, annotator management, and linguistic analysis. The remainder was a collaboration with my coauthors.
Finally, in chapter 4, through a new project, I address the systematic ambiguity of why-questions, uncovering semantic features that dictate their ambiguity and examining how they interact with state-of-the-art VQA models.
Through empirical analysis and experimentation, I contribute to a deeper understanding of how ambiguity and vagueness shape the landscape of visual question answering, paving the way for enhanced model performance and alignment with human cognition
DEVELOPMENT AND EVOLUTION IN THE OLFACTORY SYSTEM OF BIRDS
Get PDFThe anatomical architecture that supports olfaction in birds exhibits an astounding degree of diversity and recent work examining the phylogenetic distribution of olfactory bulb size and its correlation with olfactory receptor gene numbers reveals a complex history in this system across crown and stem birds. Revealing the evolutionary history of this sensory modality in birds is currently restricted by only a basic understanding of the comparative anatomy and development of the avian olfactory system. In this thesis, I aim to expand the parameters of this limited understanding through documentation and comparative analysis of the avian olfactory system in ontogeny and phylogeny. I examine growth and scaling relationships in olfactory structures (olfactory turbinates and olfactory bulbs) and their adjoining anatomy (respiratory turbinates, cerebrum, and whole brain) through embryogenesis in three taxa: Gallus gallus (chickens), Coturnix japonica (Japanese quail), and Anas platyrhynchos (ducks). I then explore how embryonic data inform scaling relationships between the olfactory turbinates and olfactory bulb across a sample of adult avian specimens bracketing the major clades of crown Aves. Discrepancies in developmental growth trajectories are significant among groups and reveal differences in olfactory growth between all three taxa. Olfactory turbinates return a higher proportion of significant growth discrepancies from other structures as compared to the olfactory bulbs. With evidence of conserved growth trajectories
between the olfactory bulb and other brain regions, the implications of concerted and mosaic evolutionary processes are discussed in relation to developmental data recovered. Temporal shifts in the growth of olfactory structures are identified as a potential for heterochronic influences on this system. Ontogenetic growth is then compared to a sample bracketing crown Aves and reveal a decoupling of covariation between the olfactory bulb and turbinates. Early diverging clades parallel the growth trajectories of ducks and the full ontogeny of chickens and show covariation between olfactory structures. This covariation is not recovered in the later diverging clade Neoaves, it is hypothesized that the developmental processes enabling this decoupling are evident in Galloanseres and were possibly primed for an evolutionary shift in developmental programs prior to the divergence of Neoaves
Barriers and Pathways to Educational Opportunity for Low-Income Families: Qualitative Evidence from an Experimental Intervention
No full textLow-income families disproportionately enroll in schools with lower levels of educational resources and academic achievement and higher levels of student poverty as compared to middle-class families. Economic school segregation is an important mechanism that contributes to inequalities in children’s educational and life outcomes.
Existing explanations for why low-income families often attend low-quality schools emphasize that high-performing schools are located in low-poverty neighborhoods where low-income families cannot afford to live. Low-income parents also face barriers to learning about high-performing schools and potential concerns over whether they provide a good fit for their children. However, evidence indicates that interventions with the potential to address barriers – housing vouchers, school choice programs, and informational interventions – have had limited efficacy. The shortcomings of these efforts indicate additional barriers constraining low-income families’ school choices that remain unexplained.
This dissertation addresses this gap in the literature by leveraging longitudinal interviews with a racially diverse sample of over 100 parents who participated in an experimental housing intervention. The intervention tested whether supplementing housing vouchers with counseling, customized search assistance, and short-term financial assistance increased the likelihood of families moving to low-poverty neighborhoods. This dissertation explores how families chose and assessed schools in this experimental context.
Findings show that the intervention had substantial success in allowing low-income families to enroll in higher-performing schools by helping them navigate housing search obstacles, interpret school information, and providing someone to vouch for school quality. Most parents described these schools as desirable, but some parents perceived potential negative consequences for children’s well-being or family life that led to some having to make difficult tradeoffs in their school choices. Higher instructional quality and more educational resources in higher-performing schools led parents to perceive their new schools as responsive to their children’s needs and, in some instances, to an increased sense of parental efficacy.
These findings clarify theories of unequal school sorting and identify conditions in which low-income families are able to realize substantial gains in school quality. In consequence, this dissertation helps explain the persistence of economic school segregation and provides important insights for future research and policy
Characterization and Microstructural Analysis of Recycled Polypropylene Films
No full textThis study aimed to explore the microstructure of recycled polypropylene (PP) films and evaluate the influence of recycling, polyethylene (PE) content, and layer multiplying elements (LMEs) on the microstructure. PP is a widely employed polymer in film production due to its notable attributes such as strength, flexibility, and resistance to damage. Nevertheless, the recycling process tends to compromise these mechanical properties. LMEs were employed in the production of these film samples to enhance layer stability. This was essential, given that the introduced layers had reduced thickness, promoting the development of more oriented crystals and aiming to achieve more uniform interfacial slip. The goal was to develop a greater understanding of the processing of recycled polymers that could either enhance or maintain the desired thermal and mechanical properties.
Three types of recycled polypropylene film materials were examined: two made from different recycled polypropylene pellets, and one composed of a 50%-50% blend of the two materials. Each film was manufactured with and without LMEs, resulting in a total of six film specimens for characterization. Differential scanning calorimetry (DSC) was conducted on these six films, with three tests each, totaling 18 tests. The DSC data allowed for the determination of melting and crystallinity temperatures for the films, as well as enthalpies of fusion, ΔHu, for the constituent materials. Additionally, the DSC data was extrapolated to approximate the percentage crystallinity for each film specimen. Polarized light microscopy (PLM) images were captured of the film cross-sections at specific orientations with respect to the film extrusion direction during processing.
The findings highlight trends in the impact of PE content on melting and crystallinity temperatures. Melting temperature data sheds light on material manufacturing conditions, while crystallinity temperature data provides direct insights into constituent material concentrations. Notably, the study observes the effect of LMEs on material thermal properties and the degree of crystallinity, leading to an increase in crystallinity in materials with substantial PE concentrations and a decrease in low PE concentrations.
Microstructural analysis of film cross-sections reveals a predominant orientation of PP in the direction of extrusion and material spreading, alongside spherulitic PE droplets and other inclusions. These observations offer valuable guidance for future developments in recycled polymer film manufacturing and lay the groundwork for comprehensive materials characterization in subsequent studies
EQUITY IN PEDIATRIC HEALTHCARE: ADDRESSING LINGUISTIC DISPARITIES AND ETHICAL OBLIGATIONS FOR IMMIGRANT FAMILIES AND SPANISH-SPEAKING CAREGIVERS
Get PDFPost-pandemic immigration rates have remained high in the United States in 2023, with many immigrant families and young children arriving from Central and South America. They encounter significant challenges, including language barriers, while navigating the immigration
and health system. These language obstacles can impede their access to healthcare services and adversely affect their overall well-being. The availability and effectiveness of resources designed to overcome language barriers vary widely and are often underestimated and used inconsistently in certain environments. Despite the availability of language assistance resources, many immigrant families, caregivers, and children continue to encounter inadequate and inefficient services. This inconsistency not only undermines the quality of services but also highlights a major public health issue, emphasizing the urgency to tackle matters of social and health justice. Adopting a prioritarian approach to decision-making, particularly by increasing the provision of in-person interpreters, represents a crucial step both as a preventive and as a responsive strategy in pediatric settings. On-site interpreters are often preferred due to their proven effectiveness in enhancing patient experiences and improving outcomes. As such, they should be acknowledged and valued as essential members of healthcare teams, and their
availability should be expanded to meet patient needs effectively. The objective is to develop an ethical decision-making framework that prioritizes the needs of the most vulnerable, guaranteeing they receive the care and resources they rightfully deserve. To address these
resource needs effectively, comprehensive actions must be implemented at multiple levels
emphasizing linguistic justice, equitable resource provision and procedural fairness
Evaluating the Stability of N-Acetyl Cysteine Formulations for Topical Ocular Delivery
No full textRetinitis Pigmentosa (RP) is a genetic disorder characterized by the progressive onset of low light blindness caused by the death of photoreceptors. The death of cone cells is accelerated by oxidative stress that exceeds the rate of natural glutathione production. N-acetyl-cysteine (NAC) and N-acetyl-cysteine ethyl ester (NACET) are glutathione precursors that have proven therapeutic effects for RP. Topical dosing of NAC and NACET formulations have shown efficacy in both genetic mouse and chemically induced rat models of RP. These studies have exhibited that NAC and NACET provide functional and structural protection of cone cells. The clinical promise of NAC/NACET as an eyedrop formulation requires a stability analysis of the drug. To analyze the degradation of NAC, a reactive oxygen species (ROS) cell assay was used to monitor efficacy and liquid chromatography–mass spectrometry (LC-MS) was used to quantify NAC concentration. We have concluded that the dimerized form of NAC (diNAC) is ineffective at mitigating ROS. The more reactive alkaline form of NAC is less stable than the acidic form, leading to a decrease in efficacy after storage. However, both the alkaline and acidic forms showed a similar amount of degradation overtime. The preservatives tannic acid (TA) and ethylenediaminetetraacetic acid (EDTA) show the most promise for stabilizing a NAC solution. Long-term storage of NAC solutions should be in the fridge, in an anerobic vessel to minimize degradation. These studies provide insight into the difference between degradation and dimerization of NAC, however further work needs to be done to get a complete understanding
IMPACTS OF EMBEDDED STUDY STRATEGY INSTRUCTION ON STUDENT ACADEMIC OUTCOMES
Get PDFCollege student academic outcomes are influenced by several factors both in and out of the classroom. The study skills a student brings into the classroom can be a deciding factor in their chances of success in college. College faculty may not have the tools they need to reach students who are struggling with their study skills. The needs assessment study revealed that students preferred to use study skills that provided limited benefits, and faculty struggle to reach students who struggle with their studies. I created a short series of lessons plan designed to improve student study skill knowledge. This explanatory mixed methods study examined levels of student satisfaction with a study strategy lesson plan embedded into a Gross Anatomy lecture course. Five students completed a survey consisting of both quantitative and qualitative questions about their experiences learning about and using the study strategies. The responses to the survey items suggested students were satisfied with the study strategy instruction and experienced academic success using them to prepare for examinations. Students also reported perceiving reduced levels of stress when it came to studying for quizzes and exams. The results support the development and implementation of embedded study strategy instruction as a method to improve student outcomes
Characterizing Polysaccharide Protein Deletion Mutants to Investigate the Capsule Assembly of Cryptococcus Neoformans
Get PDFC. neoformans is one of a few fungal species that are encapsulated with a polysaccharide (PS) capsule. The cryptococcal capsule has been studied for its biological and physicochemical attributes that play a multifaceted role in the fungal pathogen’s survival, interaction with the immune system, and virulence. The cryptococcal capsule is composed of GXM, GXMGal, and mannoproteins. The genes involved in biosynthesis, transport, and maintenance of the capsular PS of C. neoformans have been identified; however, the later part of the capsular PS synthesis on how the capsular PS assemble to form a three-dimensional structure capsule still remains unknown. The goal of this research is to investigate the unknown part of capsular PS synthesis. Liu et al. systematically analyzed relevant collections of knockout strains associated with C. neoformans’ virulence regarding capsule formation, melanization, and thermotolerance. This study focuses on the three PS protein-coding genes (CNAG_05188, CNAG_02975, and CNAG_04320) using deletion strains from the Madhani collection, a subset of the knockout strain library by Liu et al. These uncharacterized proteins are associated with glycosyltransferases (GT) with carbohydrate-active enzyme activity (assigned to the CAZy family) speculated to be involved with capsule formation. In this study, we further characterize these PS-associated proteins to assess how these genes/proteins involved in capsule formation affect the underlying mechanisms of capsule assembly. The hypothetical protein CNAG_05188 is assigned glycogen subfamily (GT-8 glycogenin) that is part of glycosyltransferase family 8, which aids in producing lipopolysaccharides and glycogen critical for cell wall integrity and an effective means of energy conservation and signaling in cells. The hypothetical protein CNAG_02975 has orthologs in the glycotransferase-32 family that regulate the formation of glycosidic bonds by facilitating the transportation of sugar molecules during the PS process. The protein CNAG_04320 encodes for polysaccharide synthase Cps1p, part of glycosyltransferase-like family 2, essential in bacterial capsule biosynthesis. This research utilized capsule-associated assays to examine the three PS-protein deletion mutants capsules’ structure, architecture, and immunologic characteristics relative to KN99 (wt). The experiments assessed their capsule size, capsule regrowth, immunofluorescence patterns, and molecular weight before and after regrowth. The results revealed a distinct phenotype observed in mutant CNAG_02975 where an increase in average capsule size was observed after regrowth—a phenotype not seen in other PS protein deletion mutants or KN99 (wt) as they did not regenerate back to their original capsule sizes post regrowth. The subsequent SEC-MALS examination compared the weight (Mw) of regrowth polysaccharides (CPS) with the original CPS, revealing a smaller Mw in regrowth CPS for CNAG_02975. It can be speculated that the hypothetical protein (CNAG_02975) acts as a repressor. The absence may result in the overproduction of smaller PS molecules, leading to an enlarged and potentially denser capsule. Linking genetic information with phenotypic expression provides insights into the genetic basis of capsule formation. Understanding the assembly of PS and the specific functions of PS protein-coding genes is crucial for developing targeted interventions or treatments