• Ankle Foot Orthosis Designs For Patient With Peroneal Nerve Damage: The Comparison Of Three Devices For Their Effectiveness In Rehabilitation

      Cai, Huan Huan
      The study involves the participation of a patient with peroneal nerve damage. The injury caused him to be unable to dorsiflex the ankle joint. His pathological gait symptoms were investigated using 2D gait motion test. The study evaluates the functionalities of three different ankle foot orthoses. Device 1 is immovable and allows no joint motions of the ankle. Device 2 allows plantarflexion and dorsiflexion motions of the ankle. Device 3 provides the same degree of freedom as device 2 with greater assistances for dorsiflexion. The first two devices are currently available in clinical practice. The goal of this research is to design and test a rehabilitation device that can help the patient to recover. Also, to determine that the device 3 is more effective than the other two. Gait motion data was recorded from two movement planes, frontal and sagittal. The results are composed of data from four different aspects: duration, cadence, range of motion, and sagittal plane gait motions. Also, there are four data collection phases, N1 to N4, for all four aspects of data. N1 is the stage before using the devices. N2 is after using the device 1, and N3 is after using the device 2, so on for N4. The range of motion results show that after using the device 1 and 2, the dorsiflexion degree decreased by -3.97° and -1.49°, respectively. For device 3, it increased by 1.67°, which implies that the device 3 can enlarge the dorsiflexion range, as opposed to the other two. The cadence data are as following: 1455, 1399, 1373, and 1348 steps/km, in the order of N1 to N4. The data demonstrates a decreasing trend, which means that the walking performances are becoming more efficient, and they are the best when using device 3. Sagittal plane gait motion data show the raw performances of the dorsiflexing muscles without wearing the devices. The analysis compares the total left ankle dorsiflexion degrees. They are listed as the following in the order of N1 to N4: -124.27°, -167.00°, -107.69°, and -62.63°. The closer the values are to zero, the greater the dorsiflexion degree. N4 has the greatest dorsiflexion degree, which indicates that the device 3 is able to strengthen the dorsiflexors more effectively than the other two.
    • Anti-intellectualism And Student Perceptions Of Higher Education / By Jarrett Daughtry Moore.

      Moore, Jarrett Daughtry
      American discourse is increasingly anti-intellectual and public discourse has colonized educational institutions from P-12 through higher education. Through a poststructural theoretical framework and using multiple methods, this qualitative study investigated the extent to which public discourse on higher education impacts the decision making of secondary students regarding college matriculation plans. This study utilized critical discourse analysis (CDA), student interviews, and standards analysis to examine anti-intellectualism in American educational institutions. The text corpus was developed through ProQuest Newspapers and Lexis Nexis search engines and was comprised of American newspaper articles and government documents from June 1, 2016 through December 31, 2016. This text corpus was analyzed through a three-step process adapted from Jäger and Maier (2016). Gifted students from a Middle Georgia high school were interviewed and the interview transcripts were coded, analyzed, and compared to the CDA results. The Georgia Standards of Excellence for US History were analyzed to determine whether state standards are conducive to creating an educational environment devoted to the development of the intellect. The data analysis found the discourse on higher education in America to be framed almost exclusively in economic terms. The three main themes from the CDA were economics, higher education policy, and P-12 college preparation. The interview data confirmed that this discourse had infiltrated the thinking of gifted secondary students as their visions of higher education were almost exclusively framed through career and job training opportunities. The standards analysis showed that the state of Georgia provides few opportunities to develop the intellect through its course content. Future studies should track the changes in discourse through the Trump administration, new media sources, and the influence of private interests in higher education.
    • "anybody Listening?": Perceptions Of African American Girls Involvement In A Community-based Delinquency Reduction Program

      Hicks-Brown, Marco Viveca
      Female adolescents represent a growing subcategory of the juvenile justice population. This growth is directly linked to adolescent females being disproportionately incarcerated for status offenses such as running away. The Georgia House Bill 242 has changed the way status offenders are held accountable for their actions. The bill called for more researched-based, community-based services. However, there were very few gender-specific community-based services for adolescent females and even fewer programs that address all the areas of need for a delinquent adolescent female. This study adds to the literature of “what works�? for adolescent females in the juvenile justice system and establishes a long-term service that will prevent adolescent females from reoffending or violating their probation. A key component to the services provided to adolescent females is education. In this capacity, this research study sought to answer the following question: 1. How do the experiences of at-risk adolescent females in a community-based program help reduce their recidivism rates? Participants, volunteers, and the founder of Savannah Youth City, Inc. were interviewed to determine the effectiveness of SYC’s program through their lived experiences and the perception of the participants on the program’s ability to reduce their recidivism rates. This study utilized a qualitative methodology. The participants were adamant that SYC was effective in reducing their delinquent behaviors despite some of the participants having recent judicial system involvement. It was the perception of the participants that SYC provided them with acceptance, validation, and a nonjudgmental environment.
    • Application Of Population Pharmacokinetic Modeling And Simulation In Anti-infective Therapy

      GOTI, VINEET
      ABSTRACT VINEET GOTI APPLICATION OF POPULATION PHARMACOKINETIC MODELING AND SIMULATION IN ANTI-INFECTIVE THERAPY Under the direction of AYYAPPA CHATURVEDULA, PH.D. AND REBECCA BURNS, PHARM.D, PH.D. The application quantitative approaches to drug research have gained acceptance over the last few decades. One such quantitative approach is population pharmacokinetic (PopPK) modeling and simulation. PopPK modeling and simulation in this dissertation has been applied to therapeutic problems and evaluate the performance of below the limit of quantitation (BQL) data handling approaches in nonlinear mixed effect models. A PopPK model is usually developed by iteratively fitting several models to clinical data and by so doing reduces the pharmacokinetic behavior of a drug to a few PopPK parameters. The PopPK approach has the ability to quantify the variability in the pharmacokinetics of the drug. This enables the application of Monte-Carlo simulation procedures to test several what if situations. In this dissertation, the PopPK modeling and simulation approach is applied to answer therapeutic and methodological problems by using the gold standard software NONMEM®. Therapeutic problems involved: 1) the evaluation of the risk of HIV transmission to an uninfected member on Truvada (fixed dose combination of emtricitabine/tenofovir) in serodiscordant relationship 2) optimization of vancomycin dosing nomogram in Emory University hospitals. PopPK models were developed for tenofovir and vancomycin using clinical data obtained from the subject population of interest. Simulations conducted using the tenofovir PopPK model revealed that protective concentrations of tenofovir were achieved at majority of the times of perceived risk of HIV exposure. The nomogram of vancomycin was optimized by iterative simulations using the developed PopPK model. The optimized nomogram incorporated a loading dose and reduced the maintenance dose. This resulted in more subjects consistently falling in the therapeutic concentration range. The methodological problem involved the evaluation of two newly suggested below the quantification limit (BQL) data handling methods: fractional conditional single imputation (FCSI) and conditional multiple imputation (CMI). These two methods were contrasted with the well accepted M3 method in terms of efficiency in estimating PopPK parameters. It was found that both CMI and FCSI were inferior to the M3 approach. The M3 method, for the most part, gave PopPK parameters with acceptable bias and precision.
    • Application of Recurrent Neural Networks for Pharmacokinetic Modeling and Simulation

      Khusial, Richard Darien; College of Pharmacy
      Pharmacometrics and the utilization of population pharmacokinetics play an integral role in model informed drug discovery and development (MIDD). Recently, there has been a growth in the application of deep learning approaches to aid in areas within MIDD. In this work, we aim to explore the potential of deep learning approaches towards drug concentration prediction and simulation. A total of 1,527 olanzapine drug concentrations sparsely sampled from 523 individuals along with eleven patient-specific covariates provided by the CATIE studies were used in model development, validation, and simulation. LSTM and LSTM-ANN with multiple inputs were investigated towards olanzapine drug concentration predictions. The LSTM-ANN model captured the relationships within a pharmacokinetic dataset and generated olanzapine drug concentration predictions with a lower RMSE than the LSTM model. Bayesian optimization was implemented to tune the hyperparameters of the LSTM-ANN model. The LSTM-ANN model had a RMSE of 29.566 in the validation set. A population pharmacokinetic model using NONMEM model was constructed as a reference to compare the performance of the LSTM-ANN model. The RMSE of the NONMEM model was 31.129. Permutation importance revealed age, sex and smoking were highly influential covariates in the LSTM-ANN model. The LSTM-ANN model showed potential in drug concentration prediction as it performed comparably to the NONMEM model. Future studies investigating clinical studies with varying sample sizes and sampling strategies are required to further examine the potential of a LSTM-ANN model towards drug concentration prediction. For olanzapine drug concentration simulations, three RNN cells within an RNN-ANN model with multiple inputs were studied. The GRU-ANN model resulted in the optimal RNN-ANN model with the lowest RMSE in the simulation data. Bayesian optimization was implemented to optimize the hyperparameters of the GRU-ANN model. The optimized GRU-ANN model resulted in a simulation RMSE of 24.844. Visual inspection revealed the simulated olanzapine drug concentrations were lower than their respected observed olanzapine drug concentrations. Exploratory data analysis revealed the underperformance may have been a result of dosing levels between the CATIE studies having little overlap. A comprehensive clinical trial study is required to fully explore the potential of a GRU-ANN model towards drug concentration simulations.
    • Applications Of Mechanistic Modeling And Simulations In Compound And Dosage Forms Selections / By Eric Akwasi Mintah

      Mintah, Eric Akwasi
      Physiologically based pharmacokinetic (PBPK) modeling and simulation techniques have been adopted in the pharmaceutical industry to aid in compound selection and dosage form development in recent years. This is a result of easier access to computers and advanced knowledge of species physiology. The mechanistic modeling approach utilizes the compound’s physiochemical properties, formulation related factors, route of administration and species physiology in order to predict the concentration-time profile in plasma and tissues. In this dissertation, different predictive and mechanistic models (ADMET®, ACAT®, OCCAT® and metabolite tracking approaches in Gastroplus®) were applied to simulate the concentration time profiles of various compounds. We applied mechanistic modeling techniques to predict the concentration-time profiles of curcumin and its analogs in order to identify potential drug candidates for future preclinical and clinical studies. An in silico based absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction tool in Gastroplus® (version 8.5, Simulations Plus, Inc., Lancaster, CA, USA) was utilized. For this purpose, we performed model qualifications by comparing the simulated pharmacokinetics data of pure curcumin and compared to the observed data from literature. Curcumin analogues and other compounds that showed higher potential for oral absorption were selected for further study. In our second project, we evaluated the predictability of the new oral cavity compartmental absorption and transit (OCCAT®) model by utilizing commercial buccal and sublingual (fentanyl, buprenorphine, nicotine, miconazole, rizaptriptan and testosterone) formulations. The new OCCATTM model was able to simulate the PK parameters/profiles of published multiple doses of buccal and sublingual drugs administered to healthy and patient population. Varying degrees of bias was observed for all the simulated PK parameter values as compared to the published parameter values for the compounds tested based on the computed % predictability error. Although, the new OCCAT model can be used to support the formulation development and regulatory decisions, its applicability and the predictability for specific drug needs to be adequately qualified. In another project, we conducted mechanistic analysis to track the metabolites of tenofovir disoproxil fumarate (TDF) using PBPK modeling. The main goal of the project was to track the pharmacokinetics of a prodrug, tenofovir disoproxil fumarate (TDF) and its parent drug, tenofovir. Finally, the mechanistic modeling approach was utilized to simulate the disposition, including potential metabolic pathways of 4-benzylpiperidine based on its predicted physiochemical properties.
    • Approaching Conflicts Over Time In Counseling Supervision: Perspectives Of Wise Minority Supervisors

      Ayers, Lindsay Nicole
      Conflicts in the counseling supervision relationship have not been given much consideration in the research literature despite the fact that they occur frequently (Quarto, 2002). The purpose of this study was to explore wise, minority supervisor’s perceptions about their approaches to conflicts in the supervisory relationship, including if and how their approaches have developed over time. Using the following research question as a guide, “What are the lived experiences of wise, minority supervisors’ growth process in approaching conflicts in supervision?” the goal was to gain an in-depth understanding of how wise minority supervisors approach conflicts and how their approach has grown or developed across their career. By examining perceptions related to these factors, supervisors received insight about approaching conflicts in supervision. Due to the lack of research concerning minority supervisor development and supervision conflicts, semi-structured interviews with wise, minority, counseling supervisors were conducted using phenomenological methods of inquiry. Transcripts were analyzed and four core themes were extrapolated from the data and discussed. Recommendations for future counseling supervision research and practice were discussed along with limitations of the study.
    • Approaching The Tomb: How Scriptural Reflection And Hospice Education Influence The Church's Conversations About Death And Dying

      Duckworth, Darian
      DARIAN ELISE DUCKWORTH APPROACHING THE TOMB: HOW SCRIPTURAL REFLECTION AND HOSPICE EDUCATION INFLUENCE THE CHURCH’S CONVERSATIONS ABOUT DEATH AND DYING Under the Direction of CHANEQUA WALKER-BARNES, Ph.D. First United Methodist Church of West Point, Mississippi, is a multigenerational congregation experiencing growth in membership. Much of the church’s energy goes into activities for those able to come to the church building. The problem that has developed is that the homebound members and those who are nearing death are at risk of feeling isolated from the community of faith. The project developed as a way to identify what might cause church members to shy away from one another’s deathbeds. The goal of the project was to provide space in the local church for conversations on dying, death, and resurrection. The project measured the effects of Bible study and hospice education on the church’s ability to talk about death and dying. The intention was to help members of the local church articulate and reflect on which components of the end of life of their loved ones evoked discomfort and unease. The seven-week project consisted of a group interview in the first session, three sessions of Bible study on John 11:17-44, two sessions of hospice education, and a group interview in the final session. The project’s methodology involved qualitative research with data collection from group interviews and discussion. Data came from the two group interviews. The type of analysis used was phenomenological inquiry. The results of the project suggested that lack of medical information about the end of life and a lack of theological reflection about death in the local church contribute to people’s fears of talking about death and dying. There was concern expressed in the group about the suffering of the human body as death nears. Developing trust and relationships, especially through storytelling, helped enable conversations in the context of a small group. The study began with asking questions of a group but has become the beginning of a conversation that the local church can continue. Further study would include expanding the hospice education to others in the congregation, perhaps in conjunction with a sermon series on life after death. I would also hope that the project could become a small group study for use in other congregations.
    • Association Of Genetic Variation And Lipid-related Concentrations In African American Men With And Without Type 2 Diabetes

      Samedy, Lesly-Anne Carline
      Abnormal levels of lipids and cholesterol in the blood lead to atherosclerosis, which can then cause cardiovascular disease (CVD). Specifically, decreased high-density lipoprotein (HDL) and increased low-density lipoproteins (LDL) increase the risk of CVD such as myocardial infarction and ischemic stroke. These lipid abnormalities occur more frequently in individuals with Type 2 diabetes mellitus (T2DM). In addition, uncontrolled diabetes causes damage to the blood vessels, in turn making them more prone to damage from atherosclerosis, putting these individuals at especially high risk for the development of CVD. African Americans with T2DM are at an even greater risk of CVD as a result of a combination of risk factors, among which dyslipidemia plays a prominent role. However, their lipid profile is often different from Caucasians with T2DM. Genetic variations in ADIPOQ, APOE, CETP, NOX3, PCSK9, and PON1 are thought to lead to altered levels of circulating LDL and HDL and may potentially explain the variability seen in lipid levels. Given the increased risk of CVD in African Americans with T2DM, it is important to gain an understanding of the underlying physiology and genetics. The goal of this study is to understand the genetic association with lipid levels in AA males with and without T2DM. Our long-term goal is to identify polymorphisms that can serve as biomarkers in the prediction, development and management of CV events in patients with both T2DM and dyslipidemia. To address each aim and analyze any potential relationships and/or interactions, we employed a candidate gene case-control approach where we compared genotype frequencies of lipid related candidate genes in unrelated African American males, 30 years of age of older, not currently treated with lipid lowering agents, with T2DM and healthy nondiabetic controls. Our data suggest that alterations in HDL and LDL particle levels are potentially due to genetic variation as well as the presence of T2DM. The CETP Taq1B B2-allele was associated with higher levels of HDL 2b and HDL L, but a lower level of HDL 3a and HDL 3b. In addition, the CETP Taq1B B2-allele was associated with decreases in small subclasses of LDL: LDL IVb, LDL IVa & LDL IIIb, where small LDL subclasses are considered more atherogenic compared to larger LDL. PON1 L55M variant allele was associated with decreases in HDL S as well as significant interactions between genotype and diabetic status on HDL 3a. The APOE E4 allele was associated with higher levels of LDL subclass: LDL 3a, LDL 2b, LDL 2a, LDL M and LDL L. With respect to PCSK9, the presence of diabetes abrogates the effects of the A443, potentiating a more atherosclerotic profile. In the absence of T2DM, levels of HDL 3a and 3b were reduced and HDL 2b elevated with the variant allele compared to the wildtype. However, we observed that, alternatively, diabetic variant allele carriers had elevated levels HDL 3a, and 3b and reduced levels of HDL 2b. The ADIPOQ variant allele was associated with lower levels of IDL 2, where lower levels of IDL potentially indicate a decrease in CVD risk. African Americans suffer disproportionately from CVD but only an estimated 50% of CVD incidence can be explained by traditional risk factors. Inclusion of genetics as well as lipoprotein subclass information may be beneficial. We observed ADIPOQ variant allele carriers had significantly lower levels of LDL 1 and IDL 2 and APOE variant allele carriers had significantly lower levels of LDL 1, subclasses considered less atherogenic than other LDL subclasses. CETP Taq1B and PON1 L55M variant allele carriers were significantly associated with HDL subclasses, where we observed increases in larger, more efficient HDL and decreases in smaller HDL. In addition, a significant interaction between genotype and diabetic status was observed, only for CETP Taq1B, PON1 L55M and PCSK9 A443T genotype. Targeting these particular genes, as well as many others known and unknown, may serve as promising interventions for all dyslipidemic individuals. Understanding the influence that co-morbidities may have in the presence of genetic variations will facilitate the design of innovative strategies for the prevention of morbid cardiovascular events via early detection of CVD risk.
    • Astrocytic Influences in the Auditory Brainstem in Fragile X Syndrome

      Warner, Katharine D; School of Medicine
      Fragile X Syndrome is one of the leading genetic causes of autism spectrum disorder. Fragile X Syndrome is associated with auditory hypersensitivity and childhood audiogenic frontal-temporal lobe seizures, which may be the result of abnormalities in the auditory nuclei found in the brainstem. The purpose of this research is to expand on preliminary findings that dysfunction in the auditory brainstem contributes to sound sensitivity and subsequently to frontal-temporal lobe seizures. To test the role of the LSO, VCN, and MNTB we examined the astrocyte function in these areas by extracting the auditory brainstem from Fmr1 KO mice and wild type mice. We then co-cultured these astrocytes with neurons from either mouse genotype to determine differences in the neuronal size, morphology, and synaptogenic factors. Our research examined the levels of SPARC, hevin, and thrombospondin-1, which are synaptic proteins found in the synapses in the auditory brainstem. Our results showed that Fmr1 KO astrocytes altered the size of WT neurons to a size comparable to a standard Fmr1 KO neuron, and Fmr1 KO astrocytes secreted significantly less SPARC than WT astrocytes. Overall, abnormal astrocyte function among Fmr1 KO mice was found to cause morphological changes in auditory brainstem neurons and differences in the amount of the SPARC found in the auditory brainstem between wild type and Fmr1 KO mice.
    • Becoming All That I Can Be: A Narrative Analysis Of African-american Students' Literacy Perceptions And Experiences In An Urban Title I School

      Wingfield, Marcia Vernise
      This narrative inquiry used the frameworks of critical literacy and culturally responsive pedagogy to understand literacy experiences of recent high school graduates. The purpose of the study was to explore the perceptions of recent African-American high school graduates’ literacy experiences throughout high school. Also, this study sought to promote educators’ acknowledgment of culturally situated and culturally diverse perceptions of African-American students’ varied literacy practices as viable contributions to the conceptualization of literacy curriculum. Through in-depth interviewing, three participants who were graduates of an urban, historically low-achieving, Title I high school told stories of their past, present, and future. Participant narratives were analyzed using the sociocultural approach to narrative analysis. Findings from this study revealed students’ varied literacy practices helped construct meaning of their experiences in school and out of school. Additionally, findings suggest building relationships throughout high school with teachers and peers cultivated increased engagement in literacy. Further, participants felt their overall high school literacy experiences prepared them for college level literacy tasks. As a contribution to the existing body of research for African Americans, this success-oriented narrative recommends pedagogical shifts in literacy instruction that not only acknowledge the social and cultural literacy practices of African American students but also incorporate multi-modal forms of literacy in the critical analysis of the dominant curriculum.
    • Beyond Borders: A Christian Ethical Response to Border Control in the United States

      Ball, Jeremy A; McAfee School of Theology
      Border control is a sociopolitical issue in the United States that has ignited heated conversation and, in some cases, caused division among U.S. citizens. In the midst of seeking solutions to better secure our nation’s borders, many have neglected the fact that there is currently a human crisis at the southwestern border. Thousands of migrant children have been separated from their families and are now forced to live in detention centers where there is a lack of food and proper shelter. There have also been numerous deaths for those attempting to cross our border. Keeping in mind the suffering, the objective of this study is to suggest a Christian ethical response to the crisis at the border. Providing a political analysis of border control and an exegetical study of biblical passages that may be applicable to the current crisis, this thesis proposes principles and policies that U.S. Christians must embrace in order to see the suffering come to an end. While border control is an issue worthy of recognition, my thesis concludes that the well-being of migrants must be prioritized above other matters and that neutrality in the midst of suffering is not a virtuous option for Christians.
    • Beyond Purity Culture: Exploring History, Implications, and Alternatives

      Howard, Shelby Duncan; McAfee School of Theology
      This thesis offers a careful examination of the history and ethical implications of the purity culture movement upon the American evangelical teenage population and offers an alternative approach coined True Love Honors. The harm experienced by many participants in True Love Waits and other evangelical purity culture programs creates a moral dilemma for the American evangelical church today to reflect and develop a new ethical framework for sexual ethics for adolescents. The purpose of this research is to explore primary and secondary accounts of purity culture to understand specific ethical problems within the movement unto research of applicable ethical frameworks and approaches that may offer the substance lacking in the current sexual ethical norm. The concluding results identify three particular areas of lack which may be redressed by an ethic informed by feminist care ethics and privileging the values of autonomy, consent, and honor. For further study, I recommend the intersection of LGBTQIA+ youth with purity culture, contemporary thought on purity culture by Joshua Harris and other public figures of the early movement, and trauma-informed study on purity culture unto victims of sexual and domestic violence.
    • Bioengineering Artificial Chromosomes For The Production Of Human Mirna

      Altherr, Delon
      Glioblastoma is a devastating disease with dismal patient outcomes. With current treatment options such as chemotherapy, radiation, and resection providing little hope to patients diagnosed with glioblastoma, research has turned to mesenchymal stem cells (MSCs) as a potential cellular delivery vehicle. The ability of MSCs to cross the blood brain barrier has increased the range of prospective treatment options available to patients with diseases like glioblastoma. Gene silencing through miRNA targeted therapy is one of the treatment options available through the utilization of MSCs. MSCs naturally package and secrete exosomes with miRNAs which have been shown to inhibit glioblastoma growth through gene silencing. Up until this point, miRNA targeted therapy has been limited to current gene therapy vectors and miRNA mimics. This project proposes an alternative to these approaches through the utilization of artificial chromosomes. The central hypothesis of this work is that artificial chromosomes can be bioengineered to produce multiple miRNAs for potential therapeutic applications. In order to test this hypothesis, a murine-derived artificial chromosome (platform ACE) was bioengineered to upregulate the expression of human miRNAs let-7b and miR124-1. The overall design of the project involved two major components. First was to identify a stable expression system for production of miRNA from the platform ACE. The second component consisted of subsequent analysis of miRNA production from the platform ACE. Findings from this project suggest that inducible vectors are more stable in the production of miRNA from artificial chromosomes compared to constituently activated vectors. Additionally, this project reports the successful transcription of the engineered miRNA constructs from the platform ACE in the Chinese Hamster Ovary (CHO) engineering cell line. Although this study was successful in producing primary transcripts from the platform ACE, this project further reports the disruption of miRNA processing beyond the initial transcript to a mature miRNA product. This study is in support of previous reports that CHO cells are ineffective in the production of mature miRNA from non-endogenous sources. Furthermore, suggesting that production of mature miRNA products must occur in species specific cell lines or with species specific flanking segments. Although more research is needed in the eventual utilization of artificial chromosomes in the production of miRNA, this project proposes an alternative to the use of current gene therapy vectors and miRNA mimics. In contrast to current approaches in miRNA targeted therapy, artificial chromosomes are stably maintained and not limited in their carrying capacity. Thereby opening the door for the potential delivery of multiple biological anti-cancer therapeutics in one cell mediated therapy vehicle. The use of artificial chromosomes has a long history for the delivery of large genetic payloads as well as multiple anticancer therapeutics. Thus, the potential of this project will allow for autonomous cell mediated therapy and targeting of multiple aberrant cell processes common to the etiology of glioblastoma.