Disease Modeling Commons^™

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 (ALDH^hi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDH^hi 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 ALDH^hi cells for therapy. ALDH^hi cells expanded for 6 days with BMS 493 showed a 2 ...

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

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

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 ...

Light Dependent Endolysosomal Defects In A Photoreceptor Model Of Alzheimer's Disease, Michelle S. Smith

Undergraduate Honors Theses

Alzheimer’s disease (AD) is a neurodegenerative disease which is the 6^th leading cause of death in the US. AD pathology is thought to be linked to the accumulation and aggregation of toxic proteins, amyloid-beta and tau. AD development and neurodegeneration is proposed to be caused by the toxic effects of these protein accumulations, specifically amyloid-beta, as postulated by the amyloid-cascade hypothesis. To study the relationship between amyloid-beta and overall neuronal health, a study was carried out using an amyloid-expressing fruit fly photoreceptor model. Using this model, toxicity of amyloid in a stressed lysosomal system induced by light, an ...

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

Biology and Medicine Through Mathematics Conference

No abstract provided.

Control Policies And Sensitivity Analysis In A Cutaneous Leishmaniasis Model: A Case Study In Cusco Region, Peru., Rocio M. Caja-Rivera, Ignacio Barradas

Biology and Medicine Through Mathematics Conference

No abstract provided.

Computational Modeling Of Contrast Sensitivity And Orientation Tuning In Schizophrenia, Steven M. Silverstein, Docia L. Demmin, James A. Bednar

MODVIS Workshop

Computational modeling is being increasingly used to understand schizophrenia, but, to date, it has not been used to account for the common perceptual disturbances in the disorder. We manipulated schizophrenia-relevant parameters in the GCAL (gain control, adaptation, laterally connected) model (Stevens et al., 2013), run using the Topographica simulator (Bednar, 2012), to model low-level visual processing changes in the disorder. Our models incorporated: separate sheets for retinal, LGN, and V1 activity; gain control in the LGN; homeostatic adaptation in V1 based on a weighted sum of all inputs and limited by a logistic (sigmoid) nonlinearity; lateral excitation and inhibition in ...

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen is ...

A Mixed-Methods Study: Self-Efficacy And Barriers To Participation In Workplace Wellness Programs, Massiel Perez-Calhoon

Dissertations

America needs a healthy workforce to sustain the country. The scourge of obesity continues to plague Americans despite government initiatives such as the Affordable Care Act and wellness programs in the workplace to combat this epidemic. However, despite initiatives to make America healthy, barriers continued to impede the nation’s health. Lack of awareness and sensitivity to what motivates individual participants versus group participants built formidable barriers to accessing all workplace employees equitably. The purpose of this study was twofold. First, the intent of this study was to explore the relationship between self-efficacy and the impact on participation and engagement ...

Persistent Neurobehavioral Traits In A Mouse Model Of Prenatal Ethanol Exposure, Jill M. Lawrence

Neuroscience Honors Papers

Fetal Alcohol Spectrum Disorders (FASD) effect an estimated 2% of the population, causing a range of symptoms: from craniofacial defects to inhibited cortical growth (May, et al., 2009; Murawski, et al., 2015). Impaired medial forebrain function apparent in FASD is associated with lifelong cognitive behavioral deficits, but these consequences may be avoided with early diagnosis and intervention (Streissguth, et al., 2004). Our goal is to identify early neurobehavioral abnormalities that persist into adulthood that could potentially serve as early indicators for FASD. Mouse models of prenatal ethanol exposure were developed using a voluntary drinking paradigm that introduced a sweetened ethanol ...

P35. Investigating The Effect Of Maternal Immune Activation On Sensory Filtering, Social Behaviour And Attention, Faraj Haddad

Western Research Forum

Background

Altered brain development is associated with many neuropsychiatric disorders like Autism Spectrum Disorder (ASD) and schizophrenia. Environmental insults can interfere with neurodevelopment, and a prominent example is maternal infection during pregnancy. Epidemiological studies show that children born to mothers who were infected during pregnancy display a higher risk of developing ASD and schizophrenia, and this effect is mainly due to the maternal immune response. Polyinosinic-polycytidilic acid (Poly I:C) is a double stranded RNA molecule that mimics viral markers and elicits an immune response. When injected in pregnant rodents, this model produces offspring that exhibit core symptoms of ASD ...

Modification Of The Ruiz-Moreno Chikungunya Seir Model, Joseph Devlin

Student Research and Creative Activity Fair

The Ruiez-Moreno CHIKV model predicts the outcome of the Chikungunya disease. Chikungunya, a disease similar to the Zika virus, is vector-borne with very little treatment for patients. This experiment looks to find ways to improve the model. The model will still need further improvement, as there is no model that can predict with full certainty. However, a method of modification has been made to expedite the process, the code has been rearranged for easy input and to minimize possibility of unwanted changes, and the control files for comparison have been created. The method to modify the model can be superimposed ...

The Battle Against Malaria: A Teachable Moment, Randy K. Schwartz

Journal of Humanistic Mathematics

Malaria has been humanity’s worst public health problem throughout recorded history. Mathematical methods are needed to understand which factors are relevant to the disease and to develop counter-measures against it. This article and the accompanying exercises provide examples of those methods for use in lower- or upper-level courses dealing with probability, statistics, or population modeling. These can be used to illustrate such concepts as correlation, causation, conditional probability, and independence. The article explains how the apparent link between sickle cell trait and resistance to malaria was first verified in Uganda using the chi-squared probability distribution. It goes on to ...

Orthogonal Decomposition Of Left Ventricular Remodeling In Myocardial Infarction, Xingyu Zhang, Pau Medrano-Gracia, Bharath Ambale-Venkatesh, David A. Bluemke, Brett R. Cowan, J. Paul Finn, Alan H. Kadish

Office of the President Publications and Research

BACKGROUND: Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices.

RESULTS: Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from ...

Perspectives On Model Forecasts Of The 2014–2015 Ebola Epidemic In West Africa: Lessons And The Way Forward, Gerardo Chowell, Cecile Viboud, Lone Simonsen, Stefano Merler, Alessandro Vespignani

Global Health Faculty Publications

The unprecedented impact and modeling efforts associated with the 2014–2015 Ebola epidemic in West Africa provides a unique opportunity to document the performances and caveats of forecasting approaches used in near-real time for generating evidence and to guide policy. A number of international academic groups have developed and parameterized mathematical models of disease spread to forecast the trajectory of the outbreak. These modeling efforts often relied on limited epidemiological data to derive key transmission and severity parameters, which are needed to calibrate mechanistic models. Here, we provide a perspective on some of the challenges and lessons drawn from these ...

Strategies For Enriching Variant Coverage In Candidate Disease Loci On A Multiethnic Genotyping Array, Stephanie Bien, Genevieve L. Wojcik, Niha Zubair, Christopher Gignoux, Alicia R. Martin, Lisa W. Martin, Page Study Investigators

Medicine Faculty Publications

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA ...

Epidemiology Of White Spot Syndrome Virus In The Daggerblade Grass Shrimp (Palaemonetes Pugio) And The Gulf Sand Fiddler Crab (Uca Panacea), Muhammad

Dissertations

Ever since the first outbreaks of White spot syndrome virus (WSSV), which causes White Spot Disease (WSD), in Asia in the early 1990s, the pathogen has been a major constraint to the profitability of the shrimp aquaculture industry across the globe. WSSV has a broad host range and is routinely detected in wild decapod crustaceans. In the present study, two common species in the tidal salt marsh along the northern coast of the Gulf of Mexico, the daggerblade grass shrimp (Palaemonetes pugio) and the Gulf sand fiddler crab (Uca panacea), were investigated for their role as reservoirs of WSSV and ...

Evolving Healthy Populations, Nina H. Fefferman

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.

Influence Of Preventive Measures To Eradicate The Spread Of The Zika Arbovirus, Pradyuta Padmanabhan, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.