Structural Basis for Clonal Diversity of the Public T Cell Response to Dominant Epitopes from Cytomegalovirus and Influenza

A diverse T cell receptor (TCR) repertoire is a prerequisite for effective viral clearance. However, knowledge of human TCR repertoire to defined viral antigens is limited. Recent advances in high-throughput sequencing (HTS) and single-cell sorting have revolutionized the study of human TCR repertoires to different types of viruses. In collaboration with the laboratory of Dr. Nan-ping Weng (National Institute on Aging, NIH), we applied unique molecular identifier (UMI)-labelled HTS, single-cell paired TCR analysis, surface plasmon resonance, and X-ray crystallography to exhaustively interrogate CD8+ TCR repertoires specific for cytomegalovirus (CMV) and influenza A (Flu) in HLA-A2+ humans. Our two CMV-specific TCR-pMHC structures and two Flu-specific TCR-pMHC structures provide a plausible explanation for the much higher diversity of CMV-specific than Flu-specific TCR repertoires in humans. Our comprehensive biochemical and structural portrait of two different anti-viral T cell responses may contribute to the future development of predictors of immunity or disease at the individual level.

THE PHYSICS OF IDEAS: INFERRING THE MECHANICS OF OPINION FORMATION FROM MACROSCOPIC STATISTICAL PATTERNS

In a microscopic setting, humans behave in rich and unexpected ways. In a macroscopic setting, however, distinctive patterns of group behavior emerge, leading statistical physicists to search for an underlying mechanism. The aim of this dissertation is to analyze the macroscopic patterns of competing ideas in order to discern the mechanics of how group opinions form at the microscopic level. First, we explore the competition of answers in online Q&A (question and answer) boards. We find that a simple individual-level model can capture important features of user behavior, especially as the number of answers to a question grows. Our model further suggests that the wisdom of crowds may be constrained by information overload, in which users are unable to thoroughly evaluate each answer and therefore tend to use heuristics to pick what they believe is the best answer. Next, we explore models of opinion spread among voters to explain observed universal statistical patterns such as rescaled vote distributions and logarithmic vote correlations. We introduce a simple model that can explain both properties, as well as why it takes so long for large groups to reach consensus. An important feature of the model that facilitates agreement with data is that individuals become more stubborn (unwilling to change their opinion) over time. Finally, we explore potential underlying mechanisms for opinion formation in juries, by comparing data to various types of models. We find that different null hypotheses in which jurors do not interact when reaching a decision are in strong disagreement with data compared to a simple interaction model. These findings provide conceptual and mechanistic support for previous work that has found mutual influence can play a large role in group decisions. In addition, by matching our models to data, we are able to infer the time scales over which individuals change their opinions for different jury contexts. We find that these values increase as a function of the trial time, suggesting that jurors and judicial panels exhibit a kind of stubbornness similar to what we include in our model of voting behavior.

Feasibility of An Online Survey Examining the Physical Activity Patterns Among South Asian Adults Residing In the United States

Background: Physical inactivity is a major risk factor for cardiovascular disease and diabetes among South Asians (SAs) - Bangladeshi, Bhutanese, Indian, Maldivian, Nepali, Pakistani, and Sri Lankan. Methods: An online survey was used to determine the feasibility of examining physical activity (PA) levels of SAs living in the US. The Social Ecological Model was the theoretical basis for identifying individual-level, social environmental, and physical environmental factors that impact PA. Results: Ethnicity, intention, self-efficacy, and perceived health benefits of PA were significantly associated with being physically active. Facilitators to PA included achieving improved health; while barriers were lack of time to exercise, unfamiliarity with PA, and nonexistent gender-specific PA facilities. Conclusions: This study showed that online surveys can be a promising tool for data collection among SAs. Health promotion programs should include education on the benefits of PA, and provide culturally sensitive facilities that support PA, especially for SA women.

Relations among Topic Knowledge, Individual Interest, and Relational Reasoning, and Critical Thinking in Maternity Nursing

Critical thinking in learners is a goal of educators and professional organizations in nursing as well as other professions. However, few studies in nursing have examined the role of the important individual difference factors topic knowledge, individual interest, and general relational reasoning strategies in predicting critical thinking. In addition, most previous studies have used domain-general, standardized measures, with inconsistent results. Moreover, few studies have investigated critical thinking across multiple levels of experience. The major purpose of this study was to examine the degree to which topic knowledge, individual interest, and relational reasoning predict critical thinking in maternity nurses. For this study, 182 maternity nurses were recruited from national nursing listservs explicitly chosen to capture multiple levels of experience from prelicensure to very experienced nurses. The three independent measures included a domain-specific Topic Knowledge Assessment (TKA), consisting of 24 short-answer questions, a Professed and Engaged Interest Measure (PEIM), with 20 questions indicating level of interest and engagement in maternity nursing topics and activities, and the Test of Relational Reasoning (TORR), a graphical selected response measure with 32 items organized in scales corresponding to four forms of relational reasoning: analogy, anomaly, antithesis, and antinomy. The dependent measure was the Critical Thinking Task in Maternity Nursing (CT2MN), composed of a clinical case study providing cues with follow-up questions relating to nursing care. These questions align with the cognitive processes identified in a commonly-used definition of critical thinking in nursing. Reliable coding schemes for the measures were developed for this study. Key findings included a significant correlation between topic knowledge and individual interest. Further, the three individual difference factors explained a significant proportion of the variance in critical thinking with a large effect size. While topic knowledge was the strongest predictor of critical thinking performance, individual interest had a moderate significant effect, and relational reasoning had a small but significant effect. The findings suggest that these individual difference factors should be included in future studies of critical thinking in nursing. Implications for nursing education, research, and practice are discussed.