Production and Purification of Highly Replication Defective HSV-1 Based Gene Therapy Vectors

Herpes Simplex Virus Type 1 (HSV-1) represents an attractive vehicle for a variety of gene therapy applications. To render this virus safe for clinical use, its cytotoxic genes must be removed without losing its ability to express transgenes efficiently. Therefore, complementing cell lines that can provide high titer virus are essential for clinical application. Manufacturing methods that can purify these vectors of host cell DNA and protein are also necessary for translation of this gene therapy strategy into clinic. In this thesis, I have developed complementing cell lines that allow propagation to up to 1E6 PFU/ml routinely for triple as well as quadruple deleted vectors which are among the most difficult to culture to high titer. Replacement of the ICP4 promoter with the VP16 enhancer element enriched ICP0 IE gene promoter resulted in higher induction levels and faster kinetics of ICP4 expression and a 10 fold increase in vector yield.Along these lines, I investigated the repressive nature of Vero cells to a quadruple IE mutant. A high throughput cell based chemical screen revealed a metal chelator, 1 10 phenanthroline, that was able to derepress EGFP expression not only from the quadruple backbone but of other ICP0 mutant viruses suggesting a unique cell state that was permissive for HSV-1 transgene expression. Interestingly, proteosome inhibition studies reveal that this pathway is essential for this effect not only in Vero cells but also normally permissive U2OS cells. Finally, a systematic study into ion exchange chromatography for purification of these vectors reveals dramatic differences in infectious yield depending on the matrix chosen. Anion exchange resins bound the virus with high affinity and require high salt concentrations to recover adequate titers. Cation exchange chromatography was able to purify HSV-1 to moderate titers while removing a majority of the host contaminating DNA and protein in accordance with FDA standards for clinical grade viral based vaccines

The relationship between configurations of the New Tech High School model and student achievement

Traditional educational environments have been documented as being potential barriers to improving student achievement. Consequently, reform models, such as the New Tech High School (NTHS), were created to enable educators to fundamentally rethink teaching and learning. The purpose of this study was to ascertain whether the NTHS, as a reform model, is an effective vehicle to increase student achievement. The study examined the relationship between NTHS models and desired outcomes of the New Tech Network (NTN) as indicated by: state proficiency exams, End of Course (EOC) exams; a college and career readiness exam, the American College Test (ACT); and, School Performance Scores (SPS). An attempt was made to determine if the participating NTHS schools have been accomplishing the intended outcomes of the NTN and if this reform model has the potential to successfully transform educational practices. Analysis and conclusions were based on results from the application of a chi-square distribution test, comparisons of calculated z scores with percentile ranks, and a Pearson product-moment correlation coefficient. The data sets used in the study were constructed from reported student achievement and principal/teacher perceptions at three NTHS schools located in northern Louisiana. The study found that there is an association between NTHS model configuration and student achievement scores on state proficiency exams. This study also determined that the participating NTHS schools reported lower student achievement scores on the college readiness indicator exam, the ACT, when compared to the Louisiana state average composite score. Likewise, the researcher found that the NTHS model configurations of Whole School Conversion (WSC) and Autonomous School (AS) both reported a SPS lower than the average Louisiana School Site SPS while the entire school of the Small Learning Community (SLC) configuration reported a higher SPS than the state average Louisiana School Site SPS. Finally, a positive correlation was found in NTHS principal/teacher perceptions of implementation of the NTN goals instructional approaches and principal/teacher perceptions of meeting the NTN desired student outcomes based upon the NTN School Success Rubric (SSR). Implications of the findings and recommendations for further research are provided

GVSU Course Scheduler

The GVSU Course Scheduler\u27s objective was to develop a program capable of expediting and simplifying the course selection process in which all students partake. The program takes the form of a chrome extension webpage, gathering the required information from user authenticated requests to the GVSU\u27s student availability registration system. By programmatically generating course combinations and computing relevant schedule metrics from this data, students are able to easily compare the very best schedule options available. Metrics such as downtime, days with classes, average start time, average end time, and back-to-back courses are incredibly useful in deciding which of these schedules will lead to academic success. All in all, this program transforms the monotonous and overwhelming task of scheduling into a quick and simple task

Virtual Reality: An Evidence-Based Guide for Occupational Therapy

Problem: Virtual reality (VR) is an emerging technology that serves to position the user in control of a virtual environment to maximize interest and function. VR is a context for intervention included in the Occupational Therapy Practice Framework: Domain and Process 3rd edition (OTPF-3; AOTA, 2014). It is crucial that occupational therapy (OT) practitioners enhance their knowledge about VR technology used by their clients to provide effective client-centered practice (AOTA, 2010). There is a lack of organization of the literature and research evidence regarding the use of VR as an intervention modality. While there has been a significant increase in recent literature supporting the use of VR in OT, there is a need for manuals and resources to guide clinicians in using VR as a therapeutic modality (Levac & Miller, 2013; Proffitt & Lange, 2015). Methods: An extensive literature review for articles regarding the use of the Xbox Kinect and Nintendo Wii within OT was conducted using five databases. Relevant data was extracted from each article related to the use of the Xbox Kinect or Nintendo Wii in intervention to synthesize the findings into charts. The construction of the charts followed the organization of the OTPF-3 (AOTA, 2014). Product: The authors of this product created an evidence-based resource to guide OT practitioners\u27 use of VR. The intended purpose of this product, Virtual Reality: An Evidence-Based Guide, is to assist OT practitioners\u27 adaptation and/or modification of VR activities to address individual client needs. Using this product as a guide to current knowledge and evidence regarding intervention in the context of VR, OT practitioners will be better equipped to make safe and effective choices. To further support development of literature regarding VR, the authors of this product recommended areas for future research

Initial Development and Verification of a Precise Orbit Determination Filter for the APEX CubeSat Mission

Current research for the Advanced Propulsion Experiment (APEX) at Missouri University of Science and Technology is focused on precise orbit and parameter determination to verify the performance of the Multi-Mode Ionic Monopropellant thruster payload. A batch filter to process dual-frequency GPS pseudoranges using the International GNSS Service precise position, clock, and phase center data products was developed. The filter estimates the dynamic states of the vehicle in conjunction with the coefficients of drag and solar radiation pressure, a constant average thrust magnitude, and the time biases of the GNSS receiver clock at each measurement epoch. Furthermore, it considers uncertainty in the vehicle attitude and mass measurement. The framework is extended to support examination of other parameters of interest. The statistical consistency of the filter is verified using a Monte Carlo analysis. The filter dynamics and measurement models are verified using AGI’s Systems Tool Kit and initial results of verification using NASA ICESat mission data are presented

Usability and Benefits of a Telehealth Pilot for Older Adults: Via a Service-Learning Technology Partnership

This study was conducted to determine the usability and benefits of telehealth in the older adult population. Eighteen residents in an assisted living facility were selected to participate in a pilot to study the effects of telehealth monitoring. Participants were engaged weekly with a new feature or health benefit of the remote healthcare system monitoring their vital signs. Results of the study concluded that the participants were receptive to the technology and sought to continue monitoring their health and wellness. Moreover, the older adults were able to learn the technology in a few sessions of training

The Fulbright International Education Administrators Seminars: Pathways to International Partnerships

While the benefits of studying abroad are well documented (e.g., Braskamp et al.; Lewis and Niesenbaum; Ludlum et al.; McCabe; Williams), honors administrators face significant challenges in internationalizing their honors programs and colleges. The U.S. Fulbright Commission, by partnering with commissions in France, Germany, India, Japan, Korea, Russia, and Taiwan to host programs for international education administrators from around the United States each year, is addressing the challenges of internationalizing American higher education. According to the Institute of International Education, the seminar in Germany in 1984–1985 was the first of its kind. Other seminars were added in 1986 (Japan), 1999 (Korea), 2012 (India), 2013 (France), and 2017 (Taiwan) (“The Power”). This chapter provides an overview of the German-American Fulbright Commission’s IEA seminar and outlines the seminar’s benefits and the opportunities it offers honors administrators working to internationalize their programs. The IEA application process requires a project statement, institutional statement, and letters of recommendation, including one from the applicant’s direct supervisor. Effective applications demonstrate an applicant’s “desire to learn about the host country’s education system as well as establish networks of U.S. and international colleagues” (“IEA Review Criteria”). The applicants’ administrative positions and willingness to share knowledge gained through the seminar are other important selection criteria. All applications are initially reviewed by a panel consisting of U.S. Fulbright IEA alumni. Applications are then forwarded to the specific country commission (in our case the German-American Fulbright Commission), which makes the final selection. All travel, accommodations, and program costs are covered by the Fulbright IEA Program

The Effect of Hip Taping on Hip and Knee Muscle Activity

Background and Purpose: It has been hypothesized that patellofemoral pain may be precipitated by weak hip abductor musculature that does not pull the pelvis and femurs into correct alignment during gait activities. The misalignment at the pelvis leads to misalignment down the kinetic chain, eventually affecting the knees. It is theorized that hip taping may aid in supporting the pelvis, thus reducing the EMG activity of the hip abductors and normalizing the alignment of the knees. The purpose of this study is to describe muscle activity and joint motion during a step-down test in subjects with and without the hip tape in place. Methods: Twenty healthy subjects (9 men, 11 women) with no history of hip or knee pathology performed a step-down test with and without hip tape in place. The EMG activity of the gluteus medius and the tensor fascia lata was recorded via surface electrodes while tibio-femoral joint valgus angles were measured using video-analysis. Data was analyzed using a paired samples t-test. Results: There was no significant difference in EMG activity of the gluteus medius for males (p=.603), females (p=.2S6), or males and females together (p=.840). There was also no significant difference in the EMG activity of the tensor fascia lata for males (p=.221), females (p=.876), or males and females together (p=.239). There was no significant difference in hip adduction values between taped and non-taped males (p=.060). There were, however, significant differences in hip adduction values between taped and non-taped females (p=.OOO) and taped and non-taped males and females together (p=.OOO). Conclusion: Hip taping may reduce the amount of hip adduction in patients and allow for a more efficient action at the patella, thus reducing anterior knee pain in patients. More studies, employing larger sample sizes, are needed to support the efficacy of hip taping in decreasing anterior knee pain