Impacts of Project-Based Service-Learning on Attitudes Towards Engineering in High School and First-Year Undergraduate Students

Interest in whether real-world problems or a service learning context increases students' academic performance and intent to find careers in engineering is gaining momentum. The belief that diverse student populations resonate with the idea that engineers can contribute to improving society is found throughout the literature, supporting the combination of service-learning with project-based courses as an instructional method that can impact identification with engineering in high school and first-year students, potentially increasing the recruitment and retention of capable and interested learners. While study of these reforms indicates many advantages, little meaningful evidence exists on the psychological and educational benefits from engaging in project-based service-learning.This thesis examines the evolving identity and attitudes towards community service for both high school and first-year engineering students engaged in project-based design, and whether a service-learning context influences these changing attitudes. Quantitative Likert-style surveys were developed from previously validated instruments and administered to students pre-to post-semester. Each participant was surveyed multiple times during their design experience, and the survey results were aggregated to offer insight into their evolving attitudes towards identity with engineering and service to the community. Using hierarchical linear modeling (HLM) methods, students' responses to survey items were analyzed by comparing students in multiple service and non-service sections of a project-based design course at the high school and first-year engineering levels. Study results indicate that a service-learning context in project-based courses positively impacts identity and attitudes towards community service in targeted underrepresented populations of high school and undergraduate students. A ceiling effect was apparent for some students at both levels, who were predisposed to high community service attitudes and identification with engineering. Based on the results of this study, K-12 and undergraduate should consider project-based service-learning engineering design experiences early and often to improve students' identification with engineering, demonstrate professional and societal relevance of engineering, and potentially increase the interest and retention of a diverse population of students, including women and minorities, into the pipeline of engineering education and engineering workforce

Intracellular Trafficking of MHC-I in Normal and HIV-1 Nef Expressing Cells.

HIV-1 establishes a chronic infection. To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and antigen presenting molecules (MHC-I). Nef binds the cytoplasmic tails of both molecules and disrupts their trafficking using separate mechanisms that are incompletely understood. We demonstrate here that these distinct mechanisms are dictated by differences in the cytoplasmic tails of CD4 and MHC-I. Despite these differences, we demonstrate that MHC-I and CD4 are ultimately targeted to the same degradative compartments via interaction of Nef with the cellular protein -COP. Moreover, we demonstrate that the N-terminal -helical and dimerization domains of Nef are required for the Nef/-COP interaction. These findings have revealed the convergence of separate degradative pathways for CD4 and MHC-I, providing insight into the mechanisms used by HIV to evade the immune response. The removal of MHC-I from the cell surface protects HIV-infected cells from cytotoxic T lymphocytes. However, complete downmodulation of MHC-I by HIV Nef would render the infected cell susceptible to NK cell-mediated destruction. This scenario may be avoided by Nef’s inability to downmodulate certain MHC-I alleles, HLA-C and HLA-E, which inhibit NK cells. In the present work, we sought to better understand the biology of HLA-C in order to discern its role in HIV infection. Compared to other classical MHC-I allotypes, HLA-C has low cell surface expression and altered intracellular trafficking. Our studies have revealed that aspects of HLA-C trafficking are controlled by both the extracellular and cytosolic domains, in both CD4+ T cells and macrophages. Interestingly, we also found that HLA-C expression is upregulated upon macrophage differentiation, revealing the possibility of previously uncharacterized roles for HLA-C in the immune system. These studies bring us closer to understanding the role of HLA-C in the immune system and in HIV infection. The studies described in this thesis further our understanding of the interplay between HIV and the host immune system and provide insight into the biology of HLA-C in T cells and macrophages. Collectively, these data contribute significantly to our knowledge in areas crucial for the development of better antiretroviral therapies and vaccine strategies.Ph.D.ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/58478/1/mschaefe_1.pd

CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription

Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I–associated polymorphisms in HIV-1 gag, pol, and nef genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity

Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703–positive individuals and their transmission recipients

HLA-B*57 is the class I allele most consistently associated with control of human immunodeficiency virus (HIV) replication, which may be linked to the specific HIV peptides that this allele presents to cytotoxic T lymphocytes (CTLs), and the resulting efficacy of these cellular immune responses. In two HIV C clade–infected populations in South Africa and Zambia, we sought to elucidate the role of HLA-B*5703 in HIV disease outcome. HLA-B*5703–restricted CTL responses select for escape mutations in three Gag p24 epitopes, in a predictable order. We show that the accumulation of these mutations sequentially reduces viral replicative capacity in vitro. Despite this, in vivo data demonstrate that there is ultimately an increase in viral load concomitant with evasion of all three HLA-B*5703–restricted CTL responses. In HLA-B*5703–mismatched recipients, the previously described early benefit of transmitted HLA-B*5703–associated escape mutations is abrogated by the increase in viral load coincident with reversion. Rapid disease progression is observed in HLA-matched recipients to whom mutated virus is transmitted. These data demonstrate that, although costly escape from CTL responses can progressively attenuate the virus, high viral loads develop in the absence of adequate, continued CTL responses. These data underline the need for a CTL vaccine against multiple conserved epitopes

HIV-1 Nef Targets MHC-I and CD4 for Degradation Via a Final Common β-COP–Dependent Pathway in T Cells

To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7+ vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, β-COP. Moreover, we demonstrate that Nef contains two separable β-COP binding sites. One site, an arginine (RXR) motif in the N-terminal α helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef

Impact of Pre-adapted HIV Transmission

Human Leukocyte Antigen class I (HLA) restricted CD8+ T lymphocyte (CTL) responses are critical to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, since these variants can also reduce intrinsic viral fitness. To address this question, we here develop a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4 decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to expression of certain HLA alleles. Thus, viral pre-adaptation exploits “holes” in the immune response. Accounting for these holes may be critical for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies requiring broad CTL responses to achieve successful eradication of HIV reservoirs

Prelinguistic Infants, but Not Chimpanzees, Communicate About Absent Entities

One of the defining features of human language is displacement, the ability to make reference to absent entities. Here we show that prelinguistic, 12-month-old infants already can use a nonverbal pointing gesture to make reference to absent entities. We also show that chimpanzees—who can point for things they want humans to give them—do not point to refer to absent entities in the same way. These results demonstrate that the ability to communicate about absent but mutually known entities depends not on language, but rather on deeper social-cognitive skills that make acts of linguistic reference possible in the first place. These nonlinguistic skills for displaced reference emerged apparently only after humans' divergence from great apes some 6 million years ago

Abstract A Collaborative Process for K-12 Engineering Curriculum Development

integration of math and science can be accomplished with well-developed, interactive engineering lesson plans that incorporate hands-on activities. Through real classroom interactions in elementary, middle and high schools, graduate engineering Fellows successfully bridge engineering subject-area content to age-appropriate education pedagogy. Supported by National Science Foundation (NSF) and Department of Education (DOE) 1 grants, the Integrated Teaching and Learning (ITL) Program has developed extensive and innovative hands-on engineering curricula focused on topics universal to K-12 science, technology and math classes. Graduate engineering Fellows are key to the successful creation of K-12 engineering curricula, through researching and writing engineering-focused lessons on a wide range of topics, such as energy, laws of motion, and electricity and magnetism. Comprehensive curricular units, comprised of up to 10 stand-alone lessons incorporating low-cost, hands-on activities, are standards-based at the state and national levels. Each curricular unit also contains math components, lesson background concepts, anticipated student outcomes and assessment suggestions