Single chain MHC trimer-based DNA vaccines for pathogen protection

CD8+ T cells play a major role in controlling infection and disease progression in many infectious diseases. Upon infection, antigen-specific CD8+ T cells are generated and mainly through their cytotoxic activity remove infected cells, therefore, pathogens. Ongoing research has identified antigenic epitopes in a vast number of pathogens and, using the identified epitopes, the induction of CD8+ T cell immune responses has been an important strategy for successful vaccines. However, most immunization approaches with class I binding peptides have failed to induce CD8+ T cell responses strong enough to prevent disease. This failure has been attributed to the lack of CD4+ T cell help and difficulty in maintaining a sufficient level of antigen presentation required for CD8+ T cell activation. To circumvent these limitations, we have developed fully assembled MHC molecules that can be expressed as membrane-bound proteins on the cell surface, termed single chain trimers: SCTs). SCTs are composed of an immunodominant peptide, β2m, and MHC I heavy chain covalently linked by 15-20 amino acid flexible linkers. Because SCTs are expressed as a single polypeptide chain, they do not require peptide processing, or chaperone-assisted peptide loading in the ER. Furthermore, antigen presentation by the SCT bypasses the need to compete with an extensive pool of endogenous peptides for peptide loading. SCTs are folded properly and T cells see SCTs comparably to native peptide/MHC I complexes. Various human and mouse class Ia and Ib MHC molecules have been engineered with epitope peptides into SCTs and proven as useful tools to monitor and modulate immune responses. Thus, SCT engineering offers a great potential as a platform for antigen-specific DNA vaccines. Although there have been several reports of SCT-based DNA vaccines generating antigen-specific CTL responses, there have been no reports of pathogen protection after DNA vaccine expression of SCTs. In this thesis, I examined the efficacy of SCT DNA vaccines for the first time in pathogen infection models. First, we developed a clinically relevant human HLA-A2 transgenic mouse model of West Nile virus: WNV) infection and demonstrated protective efficacy of a HLA-A2 SCT DNA vaccine against lethal viral infection. Second, I validated the potency of a SCT DNA vaccine using the BALB/c model of Listeria monocytogenes infection, which indicated that SCT DNA vaccines also provide protective immunity against bacterial infection. Lastly, I demonstrated that further engineering of SCTs: dtSCT) using a disulfide trap to better accommodate epitopes can potentiate the capacity of SCTs to stimulate CD8+ T cells, suggesting broad application of SCTs even with low immunogenic peptides. I also used disulfide trap- or chimeric SCTs to test the mechanism of antigen presentation after DNA vaccination. My studies showed that SCTs are presented to T cells as intact molecules after DNA immunization, suggesting direct presentation by transfected DCs or cross-dressing as a major mechanism of the antigen presentation by DNA vaccine. In summary, these dissertation studies demonstrated that SCT-based DNA vaccines can provide pathogen protection and SCTs are effective probes for dissecting mechanisms of antigen presentation

Classroom Atmosphere: Does it reflect one’s culture?

This article is written in order to find out whether the classroom atmosphere would reflect one’s certain culture and how cultural values would be reflected on student’s attitude in a class setting through observing and comparing the classroom atmosphere in two different countries, South Korea and the U.S

The Mindful Athlete Program

According to the spring 2020 NCAA Well-Being Study, collegiate student-athletes reported experiencing mental health concerns due to the impact of the COVID-19 pandemic. The data indicated that student-athletes were experiencing mental health concerns 150%-250% higher than historically reported (NCAA, 2020). These concerns were prevalent among all divisions. For Division III student-athletes, mental health concerns experienced during the COVID-19 pandemic included “feeling overwhelmed by all they had to do, sleep difficulties, feeling mentally exhausted, feeling very lonely, feeling a sense of loss, and feeling very lonely and sad” (NCAA, 2020). This study indicated desired resources of Division III student-athletes included elements such as “maintaining physical fitness, mental health, and staying connected socially” (NCAA, 2020)

The effect of modeling a jigsaw task on communicative strategies of ESL learners

This study examines one aspect of task-based language instruction, an increasingly popular approach, which provides learners practice in performing communicative acts in English and which promotes learners\u27 ability to use communicative strategies when problems are encountered (Long 1983; Pica 1996; Tarone & Yule 1995). This study addresses the question of whether or not a video of native speakers of English (NSE) interacting during a jigsaw task positively affects the communicative strategies of English as a Second Language (ESL) learners involved in a similar task. Two experiments were conducted. A video model showing two NSE using communicative strategies including confirmation and comprehension checks during a jigsaw task was shown to ten advanced learners of English before they performed a similar task. This group was compared with a control group of learners (N = 10) who were not shown the video. The second experiment examined how modeling may affect different proficiency levels. Twelve Korean students had a high proficiency level (mean = 601 on TOEFL) and Eight Korean students had a lower proficiency level (mean = 516 on TOEFL). For the data analysis, the utterances of participants during interaction were transcribed, and three communicative strategies (clarification requests, confirmation/comprehension checks) were coded and analyzed. The results indicate that modeling appeared to increase the communicative strategies of the experimental groups, with an apparently stronger influence on the high proficiency learners. The results suggest that video modeling of communicative strategies may be an effective method for enhancing the teaching of ESL/EFL communication strategies

Sex-Specific Associations Among Total Bone-Specific Physical Activity Score, Aortic Parameters, And Body Composition in Healthy Young Adults

Background/Objective: Physical inactivity is one of the major cardiovascular disease risk factors; however, not much is known regarding lifetime bone-specific physical activity and arterial stiffness. The aim of this cross-sectional study was to determine whether total bone-specific physical activity score (tBPAQ) was related to arterial stiffness and body composition in healthy young adults. Methods: Healthy young women (n = 56, 20.3 ± 1.3 years) and men (n = 52, 21.0 ± 1.2 years) between 18 and 25 years were recruited for this study. The tBPAQ was used to obtain a comprehensive account of lifetime bone-loading physical activity. We measured the carotid to femoral pulse wave velocity (cfPWV) to evaluate arterial stiffness using the novel oscillometric device (SphygmoCor XCEL). Dual energy X-ray absorptiometry was used to measure bone free lean body mass (BFLBM, kg) and % total body fat. Results: Partial correlations analyses showed a significant inverse relationship between tBPAQ and cfPWV (r = - 0.371, p = 0.007) in young women; however, this relationship was not found in young men (p \u3e 0.05). There were significant negative correlations between tBPAQ and % total body fat in both young women (r = - 0.265, p = 0.048) and men (r = - 0.327, p = 0.018). No significant relationships were found between tBPAQ and BFLBM (p \u3e 0.05). Conclusion: Our study provides preliminary evidence of sex-specificity of negative relationships of tBPAQ with i) cfPWV (women only) and ii) % total body fat (men and women). Whether bone-loading physical activity can lead to better cardiometabolic outcomes needs to be examined

EFFECTS OF YOGA EXERCISE ON BONE DENSITY AND BONE METABOLISM IN PREMENOPAUSAL WOMEN

Although the beneficial effects of Yoga for increasing psychological well-being and decreasing stress and reducing cardiovascular risks have been reported, no studies to date have examined intervention Yoga training to investigate its effects on bone metabolism and hormone responses. PURPOSE: The purpose of this study was to examine the effects of an 8 month Yoga exercise program on bone biomarkers, areal bone mineral density (aBMD) for the total body, dual proximal femur, and lumbar spine and volumetric bone mineral density (vBMD) for the tibia and forearm in premenopausal women. A secondary purpose was to examine IGF-I, body composition, and muscular strength changes. METHODS: Thirty-four healthy women were randomly assigned either to a Yoga group (YE, n=16, mean age; mean±SD, 45.73±3.82) or a control group (CON, n=18, 43.22±4.16). Subjects in YE group performed 60 minutes of an Ashtanga Yoga series two times per week with one day between sessions for 8 months in morning sessions (6:30 - 7:30 am, Mondays/Wednesdays). Each Yoga session consisted of 15 minutes of warm-up exercises, 35 minutes of Ashtanga Yoga postures and 10 minutes of cool-down with relaxation. Session intensity was progressively increased during the 8 months. Subjects in CON group did not receive the Yoga exercise intervention, and they were encouraged to maintain their normal daily lifestyle monitored by the bone-specific physical activity questionnaire at 2 month intervals for 8 months. Bone formation (bone alkaline phosphatase, Bone ALP) and bone resorption (tartrate-resistant acid phosphatase, TRAP5b) were assessed at baseline and after Yoga intervention. aBMD and vBMD were measured using DXA and pQCT, respectively. Body composition (DXA) and muscle strength (1RM) for leg press (LP), knee extension (KE), knee flexion (KF), lat pull down (LPD), shoulder press (SP), and biceps curl (BC) were measured. RESULTS: There were no significant differences between the groups in age, height, and weight at baseline. A significant group õ time interaction was detected in serum Bone ALP (p0.05) in percent changes for TRAP5b and ratio of Bone ALP to TRAP5b, but there was a trend (p=0.061) for serum TRAP5b, which increased slightly in YE group whereas it decreased in CON group (1.0±4.6% vs. -8.3±6.5%). No significant BMD differences and percent changes were detected in the total body, lumbar spine, and dual femur sites between groups (p>0.05). However, a group õ time interaction was detected (p0.05). However, a significant time effect was detected (p0.05). No significant differences and percent changes in weight, total fat mass, and %fat were detected (p>0.05). However, bone free lean body mass in both groups significantly increased (p0.05). Also, two-way mixed factorial ANOVA with repeated measures detected a significant time effect (p0.05) after the 8 months. CONCLUSION: The findings of this study suggest that the 8 month Ashtanga Yoga was able to generate sufficient mechanical loading forces to elicit increases in bone formation (Bone ALP) as well as increases in leg press muscle strength in premenopausal women

Microscopic traffic models, accidents, and insurance losses

The paper develops a methodology to enable microscopic models of transportation systems to be accessible for a statistical study of traffic accidents. Our approach is intended to permit an understanding not only of historical losses but also of incidents that may occur in altered, potential future systems. Through such a counterfactual analysis, it is possible, from an insurance, but also from an engineering perspective, to assess the impact of changes in the design of vehicles and transport systems in terms of their impact on road safety and functionality. Structurally, we characterize the total loss distribution approximatively as a mean-variance mixture. This also yields valuation procedures that can be used instead of Monte Carlo simulation. Specifically, we construct an implementation based on the open-source traffic simulator SUMO and illustrate the potential of the approach in counterfactual case studies

An Application of Product-Service System Development Methodology in Development of Smart Home Appliances

Industrial DesignWith the diffusion of smartphones, smart products are taking deep root within our lives. Considering the high-end smart home appliances displayed at international electronics shows, smartness is being regarded as one of the most critical criteria to judge the competitiveness of manufacturing companies not only for IT devices but also for home appliances. Reflecting this tendency, many global home appliance manufacturers are devoting effort to Smart Home Appliance (SHA) development. In many cases, however, smart functions cannot provide users with significant added values because of technology-oriented approaches. Without a clear understanding on the notion of smartness, developmental strategy, and relevant methodologies, it is hard to develop genuine SHAs which effectively address users’ needs by providing differentiated values. Defined as marketable systems of products and services capable of fulfilling a user’s demand, Product-Service System (PSS) can provide SHAs manufacturers with an innovative approach to develop solution that address users’ needs in more effective ways and raise market competitiveness through offering both products and services. By shifting from sales-oriented business model to PSS, companies can perform better in terms of environmental, social and economic sustainability. Nonetheless, switching the business model based on manufacturing into a PSS model is a challenging approach for manufacturing companies because of differences between offering products and services. Underlying hypothesis of this research is that PSS development methodology can contribute to SHA development. As the first step to prove this hypothesis, the developmental direction of SHA and various PSS development methodologies were explored through literature reviews. A unified PSS methodology was proposed and the relevance of its application to SHA development inquired through expert interviews. In the expert interview the stages of existing SHA development processes which need to be reinforced with PSS development methodology were identified. Based on the findings from diagnosis, a set of tools to reinforce the SHA development processes were selected and their effectiveness identified through the workshop with practitioners. Through the entire process, the potential of PSS development methodology for SHA development was recognized and the points to be improved to support SHA development better were suggested.ope