Medicine and Health Sciences Commons^™

Targeting The Folate Receptor: Improving Efficacy In Inorganic Medicinal Chemistry, Pauraic Mccarron, Aisling Crowley, Denis O'Shea, Malachy Mccann, Orla L. Howe, Mary Hunt, Michael Devereux

Articles

The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor’s overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established. The application of inorganic folate-targeted drugs offers significant potential to expand and enhance this therapeutic approach. From the data made available to date, …

Enabling Quantification Of Protein Concentration In Human Serum Biopsies Using Attenuated Total Reflectance – Fourier Transform Infrared (Atr-Ftir) Spectroscopy, Kate Spalding, Franck Bonnier, Clément Bruno, Hélène Blasco, Ruth E. Board, Isabelle Benz-De-Bretagne, Hugh Byrne, Holly J. Butler, Igor Chourpa, Pretheepan Radhakrishnan, Matthew J. Baker

Articles

Changes in protein concentrations within human blood are used as an indicator for nutritional state, hydration and underlying illnesses. They are often measured at regular clinical appointments and the current analytical process can result in long waiting times for results and the need for return patient visits. Attenuated total reflectance – Fourier transform infrared (ATR-FTIR) spectroscopy has the ability to detect minor molecular differences, qualitatively and quantitatively, in biofluid samples, without extensive sample preparation. ATR-FTIR can return an analytical measurement almost instantaneously and therefore could be deemed as an ideal technique for monitoring molecular alterations in blood within the clinic. …

Securing The Internet Of Healthcare, Michael Mattioli, Scott J. Shackelford, Steve Myers, Austin Brady, Yvette Wang, Stephanie Wong

Articles by Maurer Faculty

Cybersecurity, including the security of information technology (IT), is a critical requirement in ensuring society trusts, and therefore can benefit from, modern technology. Problematically, though, rarely a day goes by without a news story related to how critical data has been exposed, exfiltrated, or otherwise inappropriately used or accessed as a result of supply chain vulnerabilities. From the Russian government's campaign to influence the 2016 U.S. presidential election to the September 2017 Equifax breach of more than 140-million Americans' credit reports, mitigating cyber risk has become a topic of conversation in boardrooms and the White House, on Wall Street and …

Geometroneurodynamics And Neuroscience, Keun-Hang Susan Yang, Menas Kafatos

Mathematics, Physics, and Computer Science Faculty Articles and Research

The Orthodox Interpretation of quantum mechanics, as developed by many physicists, particularly John von Neumann, addresses the role of measurement, available choices and response of the quantum system to questions posed by an observer in specific quantum laboratory experiments. As such, it is, more consistent and clearer than other interpretations of quantum mechanics and it provides an account of the interactions of observers with the external world. However, in order to explore whether quantum mechanics plays a role in the brain, which is the primary issue, one has to examine the applicability of Hilbert space structure as a valid geometric …

Structure Of The Picornavirus Replication Platform: A Potential Drug Target For Inhibiting Virus Replication, Meghan Suzanne Warden

Chemistry & Biochemistry Theses & Dissertations

Picornaviruses are small, positive-stranded RNA viruses, divided into twelve different genera. Members of the Picornaviridae family cause a wide range of human and animal diseases including the common cold, poliomyelitis, foot and mouth disease, and dilated cardiomyopathy. The picornavirus genome is replicated via a highly conserved mechanism involving a presumed cloverleaf structure located at the 5’ noncoding region of the virus genome. The 5’ cloverleaf consists of three stem loops (B, C, and D) and one stem (A), which interact with a variety of virus and host cell proteins during replication. In this dissertation, human rhinovirus serotype 14 (HRV-14) SLB …

Genotypic Responses Of Brachiaria Grass (Brachiaria Spp.) Accessions To Drought Stress, Duncan Cheruiyot, Charles Aura Odhiambo Midega, Johnnie Van Den Berg, John Anthony Pickett, Zeyaur Rahman Khan

All Peer-Reviewed Publications

Background and Objective: Brachiaria, a warm season C4 grass, is rapidly gaining popularity as fodder crop in Africa where it is also used as a component of a habitat management strategy for maize stem borers. However, increasing drought limits productivity of this grass species. The aim of this study was to evaluate and select high yielding brachiaria genotypes under simulated drought conditions. Materials and Methods: The morphological and physiological performance of 18 apomictic accessions of brachiaria in simulated drought conditions in a screen house were evaluated. Plants were exposed to different watering regimes. Well-watered (control) plants were watered every 48 …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

Environmental And Genetic Factors Affecting Antibiotic Resistance Of Extended Spectrum Î?-Lactamase Bacteria From The Rio Grande River In El Paso, Tx And Cd. Juarez, Mexico, Maria D. Fuentes

Open Access Theses & Dissertations

Background: The Rio Grande River provides a major source of potable and agricultural water for the population of the Texas/Mexico border region. Cattle farming and ranching are the most prevalent activities, which may contribute to the microbial burden of pharmaceuticals into our state's water resources. Antibiotics, presumably released into the environment by discharges originating from waste-water treatment plants, septic disposal systems, animal feeding operations and urban runoff have a definite impact on the ecosystem and may contribute to an increase in antibiotic resistance. We hypothesized that waters of the Rio Grande River contained Multi Drug Resistant Organisms (MDRO) and mobile …

The Effect Of Rare Variants In Trem2 And Pld3 On Longitudinal Cognitive Function In The Wisconsin Registry For Alzheimer's Prevention, Corinne D. Engelman, Burcu F. Darst, Murat Bilgel, Eva Vasiljevic, Rebecca L. Koscik, Bruno M. Jedynak, Sterling C. Johnson

Mathematics and Statistics Faculty Publications and Presentations

Recent studies have found an association between functional variants in TREM2 and PLD3 and Alzheimer's disease (AD), but their effect on cognitive function is unknown. We examined the effect of these variants on cognitive function in 1449 participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of initially asymptomatic adults, aged 36–73 years at baseline, enriched for a parental history of AD. A comprehensive cognitive test battery was performed at up to 5 visits. A factor analysis resulted in 6 cognitive factors that were standardized into z scores (∼N [0, 1]); the mean of these z scores was …

Simulations For Designing And Interpreting Intervention Trials In Infectious Diseases., M Elizabeth Halloran, Kari Auranen, Sarah Baird, Nicole E Basta, Steven E Bellan, +Several Additional Authors

Global Health Faculty Publications

BACKGROUND: Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods.

DISCUSSION: Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, …

Atomistic Simulations And Network-Based Modeling Of The Hsp90-Cdc37 Chaperone Binding With Cdk4 Client Protein: A Mechanism Of Chaperoning Kinase Clients By Exploiting Weak Spots Of Intrinsically Dynamic Kinase Domains, John Czemeres, Kurt Buse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A fundamental role of the Hsp90 and Cdc37 chaperones in mediating conformational development and activation of diverse protein kinase clients is essential in signal transduction. There has been increasing evidence that the Hsp90-Cdc37 system executes its chaperoning duties by recognizing conformational instability of kinase clients and modulating their folding landscapes. The recent cryo-electron microscopy structure of the Hsp90-Cdc37- Cdk4 kinase complex has provided a framework for dissecting regulatory principles underlying differentiation and recruitment of protein kinase clients to the chaperone machinery. In this work, we have combined atomistic simulations with protein stability and network-based rigidity decomposition analyses to characterize dynamic …

Virtual Reality As A Training Tool To Treat Physical Inactivity In Children, Adam W. Kiefer, David Pincus, Michael J. Richardson, Gregory D. Myer

Psychology Faculty Articles and Research

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial …

The Role Of Catalytic Residue PKA On The Hydrolysis/Transglycosylation Partition In Family 3 Β-Glucosidases, Inacrist Geronimo, Christina M. Payne, Mats Sandgren

Chemical and Materials Engineering Faculty Publications

β-Glucosidases (βgls) primarily catalyze the hydrolysis of the terminal glycosidic bond at the non-reducing end of β-glucosides, although glycosidic bond synthesis (called transglycosylation) can also occur in the presence of another acceptor. In the final reaction step, the glucose product or another substrate competes with water for transfer to the glycosyl-enzyme intermediate. The factors governing the balance between the two pathways are not fully known; however, the involvement of ionizable residues in binding and catalysis suggests that their pK_a may play a role. Through constant pH molecular dynamics simulations of a glycoside hydrolase Family 3 (GH3) βgl, we …

Long-Term Outcomes After Elective Sterilization Procedures — A Comparative Retrospective Cohort Study Of Medicaid Patients, Rachel Steward, Patricia Carney, Amy Law, Lin Xie, Yuexi Wang, Huseyin Yuce

Publications and Research

Objectives: The objectives were to compare the long-termoutcomes, including hysterectomy, chronic pelvic pain (CPP) and abnormal uterine bleeding (AUB), in women post hysteroscopic sterilization (HS) and laparoscopic tubal ligation (TL) in the Medicaid population.

Study design: This was a retrospective observational cohort analysis using data from the US Medicaid Analytic Extracts Encounters database.Women aged 18 to 49 years with at least one claimfor HS (n=3929) or TL (n=10,875) between July 1, 2009, through December 31, 2010, were included. Main outcome measures were hysterectomy, CPP or AUB in the 24 months poststerilization. Propensity score matching was used to control for patient …

Of Rats And Men, Thomas S. Walsh

Capstones

This capstone is a data-driven investigation into New York City's rat problem. By using publicly available government data to map rat activity in NYC, I identified several socio-economic variables that correlate with rat populations at the community district, borough, and city-scale. I used these findings (mainly that rat problems are linked to lower incomes) as the basis of an investigation, which includes interviews with residents, experts, and city officials. Prof. Bobby Corrigan, urban rodentologist and formerly with the NYC Department of Health criticizes the city's efforts for the first time on the record.

https://thomasseiyawalsh.wixsite.com/ratstone

The Future Of Nuclear Security: A Medical Physicist’S Perspective, Katharine E. Thomson

International Journal of Nuclear Security

Planning for the future of nuclear security is a vital and complex task, requiring cooperation and contribution from many disciplines and industries. This diversity of expertise should include the medical sector, which faces many of the same challenges as the nuclear industry: controlling access to dangerous material, creating a strong security culture, cooperating with the wider world and engaging the public.

Medical physicists, of which the author is one, oversee all aspects of small-scale radiation use. This paper discusses three key areas increasingly important to both medical and nuclear uses of radioactive materials: public engagement, prevention of nuclear and radiological …

Fluoroethoxy-1,4-Diphenethylpiperidine And Piperazine Derivatives: Potent And Selective Inhibitors Of [3H]Dopamine Uptake At The Vesicular Monoamine Transporter-2, Emily R. Hankosky, Shyam R. Joolakanti, Justin R. Nickell, Venumadhav Janganati, Linda P. Dwoskin, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [³H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [³H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [³H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [³H]DA uptake at VMAT2, with Ki values in the nanomolar range (K_i = 0.014–0.073 μM). Compound 15d exhibited the highest affinity (K_i = 0.014 μM) at VMAT2, and had 160-, 5-, …

Two-Component Hydrogel As Biomimetic Vitreous Substitutes, Sruthi Santhanam

McKelvey School of Engineering Graduate Student Theses & Dissertations

The vitreous humor of the eye is a biological hydrogel principally composed of fibrillary collagen interspersed with semi-flexible polyelectrolyte, hyaluronic acid (HA). Certain pathological conditions necessitate its removal and replacement. Current vitreous substitutes, such as silicone oils and perfluorocarbons, are hydrophobic, do not resemble the properties of the vitreous, and have known complications. An ideal vitreous substitute should have properties of the natural vitreous, perform its functions, and be biocompatible in the eye. Inspired by the structure and composition of the natural vitreous, we used bio-mimicry to develop an injectable two-component hydrogel. The hydrogel is composed of a fibrillary gellan, …

The Ability Of Different Imputation Methods To Preserve The Significant Genes And Pathways In Cancer, Rosa Aghdam, Taban Baghfalaki, Pegah Khosravi, Elnaz Saberi Ansari

Publications and Research

Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM) method was applied to detect the significant genes in rectal and lung cancers to showcase …

Long-Term Follow-Up Of Cardiac Function And Quality Of Life For Patients In Nsabp Protocol B-31/Nrg Oncology: A Randomized Trial Comparing The Safety And Efficacy Of Doxorubicin And Cyclophosphamide (Ac) Followed By Paclitaxel With Ac Followed By Paclitaxel And Trastuzumab In Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2, Patricia A. Ganz, Edward H. Romond, Reena S. Cecchini, Priya Rastogi, Charles E. Geyer Jr., Sandra M. Swain, Jong-Hyeon Jeong, Louis Fehrenbacher, Howard M. Gross, Adam M. Brufsky, Patrick J. Flynn, Tanya A. Wahl, Thomas E. Seay, James L. Wade Iii, David D. Biggs, James N. Atkins, Jonathan Polikoff, John L. Zapas, Eleftherios P. Mamounas, Norman Wolmark

Markey Cancer Center Faculty Publications

Purpose

Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment.

Patients and Methods

Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported …

Bayesian Prediction Intervals For Assessing P-Value Variability In Prospective Replication Studies, Olga A. Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin

Biostatistics Faculty Publications

Increased availability of data and accessibility of computational tools in recent years have created an unprecedented upsurge of scientific studies driven by statistical analysis. Limitations inherent to statistics impose constraints on the reliability of conclusions drawn from data, so misuse of statistical methods is a growing concern. Hypothesis and significance testing, and the accompanying P-values are being scrutinized as representing the most widely applied and abused practices. One line of critique is that P-values are inherently unfit to fulfill their ostensible role as measures of credibility for scientific hypotheses. It has also been suggested that while P-values …

Note From The Editorial Board

Dartmouth Undergraduate Journal of Science

No abstract provided.

Fetal Growth Restriction: Case Definition & Guidelines For Data Collection, Analysis, And Presentation Of Immunization Safety Data, Sarah Rae Easter, Linda O. Eckert, Nansi Boghossian, Rebecca Spencer, Eugene Oteng-Ntim, Christos Ioannou, Manasi Patwardhan, Margo S. Harrison, Asma Khalil, Michael Gravett, Robert Goldenberg, Alastair Mckelvey, Manish Gupta, Vitali Pool, Stephen C. Robson, Jyoti Joshi, Sonali Kochhar, Tom Mcelrath

Faculty Publications

No abstract provided.

Small For Gestational Age: Case Definition & Guidelines For Data Collection, Analysis, And Presentation Of Maternal Immunisation Safety Data, Elizabeth P. Schlaudecker, Flor M. Munoz, Azucena Bardají, Nansi S. Boghossian, Asma Khalil, Hatem Mousa, Mirjana Nesin, Muhammad Imran Nisar, Vitali Pool, Hans M.L. Spiegel, Milagritos D. Tapia, Sonali Kochhar, Steven Black

Faculty Publications

No abstract provided.

Pretargeting Of Internalizing Trastuzumab And Cetuximab With A 18f-Tetrazine Tracer In Xenograft Models, Outi Keinänen, Kimberly Fung, Jacob Pourat, Vilma Jallinoja, Delphine Vivier, Nagavara Kishore Pillarsetty, Anu J. Airaksinen, Jason S. Lewis, Brian M. Zeglis, Mirkka Sarparanta

Publications and Research

Background: Pretargeting-based approaches are being investigated for radioimmunoimaging and therapy applications to reduce the effective radiation burden to the patient. To date, only a few studies have used short-lived radioisotopes for pretargeting of antibodies, and such examples with internalizing antibodies are even rarer. Herein, we have investigated pretargeting methodology using inverse electron-demand Diels-Alder (IEDDA) for tracing two clinically relevant, internalizing monoclonal antibodies, cetuximab and trastuzumab.

Results: Bioorthogonal reaction between tetrazine and trans-cyclooctene (TCO) was used for tracing cetuximab and trastuzumab in vivo with a fluorine-18 (t½ = 109.8 min) labelled tracer. TCO-cetuximab or TCO-trastuzumab was administered 24, 48, or 72 …

Progression Magazine, 2017 Winter, Coastal Carolina University

Progression Magazine

Magazine of the College of Science at Coastal Carolina University.

An Analysis Of Operant Conditioning And Its Relationship With Video Game Addiction, Daniel Vu

ART 108: Introduction to Games Studies

A report published by the Entertainment Software Association revealed that in 2015, 155 million Americans play video games with an average of two gamers in each game-playing household (Entertainment Software Association, “Essential Facts about the Computer and Video Game Industry”). With this massive popularity that has sprung alongside video games, the question must be asked: how are video games affecting today's people? With the current way some video games are structured, the video game rewards players for achieving certain accomplishments. For example, competitive video games reward players who achieve victories by giving them a higher ranking or other games display …

Canines For Disabled Kids, Erin Jerrett, Margarita Mnatsakanyan, Colleen Reynolds, Yin Wang

School of Professional Studies

Canines for Disabled Kids have been working on behalf of children and their families to educate communities and promote service dog partnerships for almost twenty years. Their advocacy with local legislatures, business owners, and community leaders highlighted the difficulties encountered when differentiating service dogs from emotional support/comfort dogs. Service dogs are entitled to access by the Americans with Disabilities Act (ADA), while emotional support/comfort dogs are not protected under the federal statute or to the same rights. Canines for Disabled Kids proposed a study to obtain a current count of licensed service dogs in the Commonwealth and investigate the feasibility …

Notes From The Director, The Mcnair Team

McNair Scholars Research Journal

No abstract provided.

Full Issue, The Mcnair Team

McNair Scholars Research Journal

No abstract provided.