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Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona 2018 University of Nebraska at Omaha

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and ...


Molecular And Functional Analysis Of Anchorage Independent, Treatment-Evasive Neuroblastoma Tumorspheres With Enhanced Malignant Properties: A Possible Explanation For Radio-Therapy Resistance, Tamara Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D. Sandler 2018 George Washington University

Molecular And Functional Analysis Of Anchorage Independent, Treatment-Evasive Neuroblastoma Tumorspheres With Enhanced Malignant Properties: A Possible Explanation For Radio-Therapy Resistance, Tamara Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D. Sandler

Genomics and Precision Medicine Faculty Publications

Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic ...


Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +several additional authors 2018 George Washington University

Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in ...


24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +several additional authors 2017 George Washington University

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9 ...


Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan 2017 The University of Western Ontario

Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan

Electronic Thesis and Dissertation Repository

Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by loss-of-function mutations in either TSC1 or TSC2. Their respective gene products regulate the mechanistic target of rapamycin (mTOR) signaling pathway, which serves as an activator of cellular proliferation, metabolism, and cell survival. Orthologs of the TSC1 and TSC2 genes exist in a wide range of organisms, including the commonly used and genetically tractable model eukaryote, Schizosaccharomyces pombe. To better understand the functional roles of S. pombe tsc1 and tsc2, I exploited recent advances in genetic interaction biology to identify and characterize genes that modulate the phenotypic effects of tsc1 ...


The Dynamics Of An Epidemiological Model For Human Papillomavirus With Partial Vaccination In A Heterogeneous Population, Stefano Chiaradonna 2017 Illinois State University

The Dynamics Of An Epidemiological Model For Human Papillomavirus With Partial Vaccination In A Heterogeneous Population, Stefano Chiaradonna

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Dftd Age Structure And Vaccination Modeling, Christopher D. Bruno 2017 University of St. Francis

Dftd Age Structure And Vaccination Modeling, Christopher D. Bruno

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


The Kinetics Of Type I Interferons During Influenza A Virus Infection, Margaret A. Myers 2017 St. Jude Children's Research Hospital

The Kinetics Of Type I Interferons During Influenza A Virus Infection, Margaret A. Myers

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Handguns And Hotspots: Spatio- Temporal Models For Gun Violence In Chicago,Il, Shelby Scott 2017 University of Tennessee, Knoxville

Handguns And Hotspots: Spatio- Temporal Models For Gun Violence In Chicago,Il, Shelby Scott

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Pathogen Modeling And You! - An Investigation Of Parameter Effects On A Bio-Mathematical Model, James Board 2017 Illinois State University

Pathogen Modeling And You! - An Investigation Of Parameter Effects On A Bio-Mathematical Model, James Board

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


The Role Of Intermittent Preventive Treatment For Malaria In Saving Lives And Promoting Drug Resistance, Carrie Manore 2017 Illinois State University

The Role Of Intermittent Preventive Treatment For Malaria In Saving Lives And Promoting Drug Resistance, Carrie Manore

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Mathematical Medicine: Modeling Disease And Treatment, Lisette dePillis 2017 Illinois State University

Mathematical Medicine: Modeling Disease And Treatment, Lisette Depillis

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Challenges In Modeling Complexity Of Neglected Tropical Diseases: A Review Of Dynamics Of Visceral Leishmaniasis In Resource Limited Settings, Swati DebRoy, Olivia F. Prosper, Austin Mishoe, Anuj Mubayi 2017 University of South Carolina - Beaufort

Challenges In Modeling Complexity Of Neglected Tropical Diseases: A Review Of Dynamics Of Visceral Leishmaniasis In Resource Limited Settings, Swati Debroy, Olivia F. Prosper, Austin Mishoe, Anuj Mubayi

Mathematics Faculty Publications

Objectives: Neglected tropical diseases (NTD), account for a large proportion of the global disease burden, and their control faces several challenges including diminishing human and financial resources for those distressed from such diseases. Visceral leishmaniasis (VL), the second-largest parasitic killer (after malaria) and an NTD affects poor populations and causes considerable cost to the affected individuals. Mathematical models can serve as a critical and cost-effective tool for understanding VL dynamics, however, complex array of socio-economic factors affecting its dynamics need to be identified and appropriately incorporated within a dynamical modeling framework. This study reviews literature on vector-borne diseases and collects ...


Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal 2017 The University of Western Ontario

Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal

Electronic Thesis and Dissertation Repository

Cellular therapy to induce islet regeneration is emerging as a novel treatment strategy for diabetes. Umbilical cord blood (UCB)-derived hematopoietic stem/progenitor cells (HSPC) isolated by high aldehyde dehydrogenase activity (ALDHhi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDHhi cells are rare and expansion without the loss of regenerative function is required. We hypothesized that BMS 493, an inverse retinoic acid receptor agonist, will prevent HSPC differentiation of HSPC during expansion, generating more ALDHhi cells for therapy. ALDHhi cells expanded for 6 days with BMS 493 showed a 2 ...


The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello 2017 George Washington University

The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello

Genomics and Precision Medicine Faculty Publications

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans.

METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age ...


Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch 2017 University of Nebraska Medical Center

Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch

Theses & Dissertations

DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4; 40% penetrance (17/42)). In contrast, mono-allelic inactivation of Dnmt3a results in the presentation of CLL ...


Application Of Support Vector Machine Modeling And Graph Theory Metrics For Disease Classification, Jessica M. Rudd 2017 Kennesaw State University

Application Of Support Vector Machine Modeling And Graph Theory Metrics For Disease Classification, Jessica M. Rudd

Grey Literature from PhD Candidates

Disease classification is a crucial element of biomedical research. Recent studies have demonstrated that machine learning techniques, such as Support Vector Machine (SVM) modeling, produce similar or improved predictive capabilities in comparison to the traditional method of Logistic Regression. In addition, it has been found that social network metrics can provide useful predictive information for disease modeling. In this study, we combine simulated social network metrics with SVM to predict diabetes in a sample of data from the Behavioral Risk Factor Surveillance System. In this dataset, Logistic Regression outperformed SVM with ROC index of 81.8 and 81.7 for ...


The Effect Of Insulin Treatment And Exercise Modality On Skeletal Muscle Fiber Size In Streptozotocin-Induced Type 1 Diabetic Rats, John Z. Nickels 2017 The University of Western Ontario

The Effect Of Insulin Treatment And Exercise Modality On Skeletal Muscle Fiber Size In Streptozotocin-Induced Type 1 Diabetic Rats, John Z. Nickels

Electronic Thesis and Dissertation Repository

Severe Type 1 Diabetes Mellitus (T1DM) is known to have several negative effects on skeletal muscle mass, a condition known as diabetic myopathy. One of these effects is the atrophy of the glycolytic muscle fibers. However, the role of intensity of insulin treatment and exercise modality in attenuating this loss in fiber cross-sectional area (CSA) specifically has yet to be determined. The purpose of this investigation was to determine the effects of 12 weeks of differing intensity of insulin therapy and exercise modality on the CSA of plantaris muscle fibers, identified by myosin heavy chain (MHC) of STZ-induced T1DM rats ...


Mechanistic Mathematical Models: An Underused Platform For Hpv Research, Marc Ryser, Patti Gravitt, Evan R. Myers 2017 George Washington University

Mechanistic Mathematical Models: An Underused Platform For Hpv Research, Marc Ryser, Patti Gravitt, Evan R. Myers

Global Health Faculty Publications

Health economic modeling has become an invaluable methodology for the design and evaluation of clinical and public health interventions against the human papillomavirus (HPV) and associated diseases. At the same time, relatively little attention has been paid to a different yet complementary class of models, namely that of mechanistic mathematical models. The primary focus of mechanistic mathematical models is to better understand the intricate biologic mechanisms and dynamics of disease. Inspired by a long and successful history of mechanistic modeling in other biomedical fields, we highlight several areas of HPV research where mechanistic models have the potential to advance the ...


Simulating Within-Vector Generation Of The Malaria Parasite Diversity, Lauren M. Childs, Olivia F. Prosper 2017 Virginia Tech

Simulating Within-Vector Generation Of The Malaria Parasite Diversity, Lauren M. Childs, Olivia F. Prosper

Mathematics Faculty Publications

Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework that ...


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