Physical Sciences and Mathematics Commons^™

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3%) cases …

Analysis Of Hiv Diversity In Hiv-Infected Black Men Who Have Sex With Men (Hptn 061), Iris Chen, Gordon Chau, Jing Wang, William Clarke, Mark A. Marzinke, Manya Magnus, +14 Additional Authors

Epidemiology Faculty Publications

Background

HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.

Methods

A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified …

Genetic Variants In Kcnj11, Tcf7l2 And Hnf4a Are Associated With Type 2 Diabetes, Bmi And Dyslipidemia In Families Of Northeastern Mexico: A Pilot Study, Hugo Leonid Gallardo-Blanco, Jesus Zacarias Villarreal-Perez, Ricardo Martin Cerda-Flores, Andres Figueroa

Computer Science Faculty Publications and Presentations

The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low‑density lipoprotein (LDL), very LDL (VLDL), high‑density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 …

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.

Impact Of Devil Facial Tumor Disease On The Tasmanian Devil Age Structure, Christopher Bruno, Vashni Vasquez

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Kinetics Of Type 1 Interferons During Influenza Virus Infection, Margaret A. Myers

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Optimal Control Of Vaccination Rate In An Epidemiological Model Of Clostridium Difficile Transmission, Brittany Stephenson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Multi-Sector Analysis Of The Progress And Challenges Of Soil-Transmitted Helminth Eradication In Rural Udaipur, Jessica Ellis

Independent Study Project (ISP) Collection

India is home to 240 million children currently at risk of Soil-Transmitted Helminthiasis, which is spread via unclean water, soil, and food, and causes acute pain and malnutrition. While acknowledging the research debates over WASH and mass drug administration, this study seeks to identify the systemic multidisciplinary issues affecting STH elimination efforts in rural Udaipur. Twenty-three interviews were conducted in villages, government departments, NGOs, and medical sectors to identify the challenges within each approach to deworming, and their experiences with multi-sectoral collaboration. The most recurring issues across disciplines were need for invested local leadership, increase in health literacy of adults, …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Optimal Control Analysis Of Ebola Disease With Control Strategies Of Quarantine And Vaccination, Muhammad Dure Ahmad, Muhammad Usman, Adnan Khan, Mudassar Imran

Mathematics Faculty Publications

The 2014 Ebola epidemic is the largest in history, affecting multiple countries in West Africa. Some isolated cases were also observed in other regions of the world.

A Bi-Stable Switch In Virus Dynamics Can Explain The Differences In Disease Outcome Following Siv Infections In Rhesus Macaques, Stanca Ciupe, Christopher Miller, Jonathan Forde

Biology and Medicine Through Mathematics Conference

No abstract provided.

Determinants Of The Efficacy Of Hiv Latency Reversing Agents And Implications For Drug And Treatment Design, Ruian Ke

Biology and Medicine Through Mathematics Conference

No abstract provided.

Using Mathematical Modeling To Unmask The Concealed Nature Of Long Qt-3 Syndrome, Steven Poelzing, Amara Greer-Short, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Optimal Insecticide-Treated Bed-Net Coverage And Malaria Treatment In A Malaria-Hiv Co-Infection Model, Eric Numfor

Biology and Medicine Through Mathematics Conference

No abstract provided.

Using Predator Carrying Capacity For A Pathogenic Vector-Dynamic Differential Model, Rosahn P. Bhattarai

Biology and Medicine Through Mathematics Conference

No abstract provided.

A Mathematical Model Of The Spread Of Dengue Fever Incorporating Mobility, Kelly A. Reagan

Biology and Medicine Through Mathematics Conference

No abstract provided.

Heterogeneous Responses To Viral Infection: Insights From Mathematical Modeling Of Yellow Fever Vaccine, James R. Moore

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Models Of Hiv And Hpv Coinfection, Samantha Erwin, Meghna Verma, Vida Abedi, Raquel Hontecillas-Magarzo, Stefan Hoops, Josep Bassaganya-Riera, Stanca M. Ciupe

Biology and Medicine Through Mathematics Conference

No abstract provided.

Global Dynamics Of A Model Of Joint Hormone Treatment With Dendritic Cell Vaccine For Prostate Cancer, Erica M. Rutter, Yang Kuang

Biology and Medicine Through Mathematics Conference

No abstract provided.

Can Including Time Delay In Epidemic Models Significantly Improve Predictions Concerning Intervention Strategies?, Adrienna N. Bingham, Leah Shaw

Biology and Medicine Through Mathematics Conference

No abstract provided.

Low Energy Defibrillation By Synchronization; 90 % Less Energy Compared To One Shock., Flavio H. Fenton, Yanyan Ji, Ilija Uzelac, Niels Otani, Elizabeth M. Cherry

Biology and Medicine Through Mathematics Conference

No abstract provided.

A Link Between Paediatric Asthma And Obesity: Are They Caused By The Same Environmental Conditions?, Phylicia Gonsalves

Electronic Thesis and Dissertation Repository

The highly associated paediatric conditions of asthma and overweight have seen dramatic increases over the past few decades. This thesis explored air pollution exposure as a potential underlying mechanism of co-morbid asthma and overweight among adolescents aged 12 to 18 years. Data from the Canadian Community Health Survey were merged with a database containing estimates of air pollution as assessed by particulate matter ≤ 2.5 microns (PM_2.5) concentrations at the postal code centroid in southwestern Ontario. Logistic regression was used to conduct the analysis. Adolescents were more likely to be overweight as PM_2.5 concentrations increased. There was …

Metabolomics Reveals New Mechanisms For Pathogenesis In Barth Syndrome And Introduces Novel Roles For Cardiolipin In Cellular Function, Yana Sandlers, Kelly Mercier, Wimal Pathmasiri, Jim Carlson, Susan Mcritchie, Susan Sumner, Hilary J. Vernon

Chemistry Faculty Publications

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via ¹H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of …

Conditional Screening For Ultra-High Dimensional Covariates With Survival Outcomes, Hyokyoung Grace Hong, Jian Kang, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in …

Inferring Causal Molecular Networks: Empirical Assessment Through A Community-Based Effort, Steven M. Hill, Laura M. Heiser, Thomas Cokelaer, Michael Unger, Nicole K. Nesser, Daniel E. Carlin, Yang Zhang, Artem Sokolov, Evan O. Paull, Dong-Chul Kim

Computer Science Faculty Publications and Presentations

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology …

Multilevel Analysis Of Individual, Neighborhood, And Health Care Facility Characteristics Associated With Achievement And Maintenance Of Hiv Viral Suppression Among Persons Newly Diagnosed With Hiv In New York City, Ellen W. Wiewel

Dissertations, Theses, and Capstone Projects

Objective

To investigate the effect of individual, health care facility, and neighborhood characteristics on achievement and maintenance of HIV viral suppression, among New York City residents aged 13 years and older diagnosed with HIV between 2006 and 2012.

Methods

I used individual-level data from the New York City HIV surveillance registry and Case Surveillance-Based Sampling, facility-level data from the surveillance registry, and neighborhood-level data from the U.S. Census and American Community Survey. The outcomes of interest were first viral suppression after diagnosis (Aims 1 and 3; ≤400 copies/mL) and virologic failure after first suppression among persons who achieved suppression (Aim …

Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco

Celia A. Schiffer

Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Screening For Peripheral Arterial Disease And Carotid Artery Disease In Patients With Abdominal Aortic Aneurysm, Cleona Gray, Patrick J. Goodman, Paul Cullen, Stephen Badger, Kevin O'Malley, Martin K. O'Donohoe, Ciarán O. Mcdonnell

Articles

Screening for concomitant atherosclerotic disease is important in cardiovascular risk reduction. This study assessed the prevalence of carotid artery disease (CAD) and peripheral arterial disease (PAD) in patients with known abdominal aortic aneurysms (AAAs). All patients with AAA attending the vascular laboratory between the January 1, 2007, and December 31, 2009, were eligible for a carotid ultrasound and measurement of ankle brachial indices. A total of 389 (305 males) patients were identified on the AAA surveillance program with a mean (±standard deviation) age of 76 (±8) years. The mean age of the males was 75.4 (±7.8) years, and the mean …