Medicine and Health Sciences Commons^™

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 …

Controlling Water Exchange Kinetics And Improving Paracest Imaging, Jacqueline R. Slack

Dissertations and Theses

Generating MR image contrast from exogenous contrast media through chemical exchange saturation transfer (CEST) offers several exciting new possibilities, such as multicolored imaging, the interleaving of pre- and post-contrast images, and the potential to perform ratiometric metabolic imaging. The major limitation of the deployment of CEST imaging is the comparatively high detection limits of exogenous agents and particularly at the low B_¹ power levels required to meet SAR requirements. The large chemical shifts afforded by paramagnetic (paraCEST) agents permit more rapid exchange kinetics and therefore potentially more effective contrast agents. Despite comparatively large chemical shifts, many Ln³⁺ DOTA-tetraamide …

Development Of Physics Curriculum For Pre-Health Students, Elliot Eckman Mylott

Dissertations and Theses

Many pre-health students are required to take introductory physics as undergraduates, though they often struggle to see the relationship between medicine and what they learn in these courses. In order to help students make that connection, reformed curriculum was adopted that teaches physics through the context of biomedicine. This dissertation will discuss the development, implementation, and assessment of the reformed curriculum for the introductory and intermediate level physics courses that targets the needs of pre-health students.

The curriculum created during this project include laboratory activities, multimedia content, and other instructional materials all of which present physics in biomedical contexts. The …

Simplified Reversed Chloroquines To Overcome Malaria Resistance To Quinoline-Based Drugs, Bornface Gunsaru, Steven J. Burgess, Westin Morrill, Jane X. Kelly, Shawheen Shomloo, Martin J. Smilkstein, Katherine May Liebman, David H. Peyton

Chemistry Faculty Publications and Presentations

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from in vitro heme binding and beta-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities.

Benzene Formation In Electronic Cigarettes, James F. Pankow, Kilsun Kim, Kevin J. Mcwhirter, Wentai Luo, Jorge O. Escobedo, Robert M. Strongin, Anna K. Duell, David H. Peyton

Chemistry Faculty Publications and Presentations

The heating of the fluids used in electronic cigarettes (“e-cigarettes”) used to create “vaping” aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine.

Novel Compound, 84f2, Inhibits Calmodulin Deficient Ryr2, Robert Carl Klipp

Dissertations and Theses

The cardiac ryanodine receptor (RyR2) plays a key role in excitation-contraction coupling (ECC). Mutations in RyR2 are known to be linked to the arrhythmogenic disorder, catecholaminergic polymorphic ventricular tachycardia (CPVT), a deadly disease which is characterized by a leak of calcium from sarcoplasmic reticulum and a decrease in calmodulin (CaM) binding. A novel drug, 84F2, shown to inhibit arrhythmias in RyR2-R176Q heterozygous CPVT mouse hearts (2.5 µg/kg), decrease spark frequency in cells derived from CPVT mice (IC₅₀ = 35 nM), and inhibit RyR2 single channel activity at low nanomolar concentrations (IC₅₀ = 8 nM). When CaM is added …