Canonical Wnt Signaling and Its Role in Cardiac Arrythmogenesis

From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 13, 05-01-2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor(s): Stacey Rentschle

A case study of the comparison between rubberized and polymer modified asphalt on heavy traffic pavement in wet and freeze environment

Ground tire rubber (GTR) usage in asphalt pavement with the dry process has gained more prominence in recent times. The objective of this work is to investigate the pavement performance of GTR-modified asphalt pavement and polymer-modified asphalt pavement on heavy volume of traffic conditions in Michigan\u27s wet and freeze environment. A suite of laboratory tests was done to evaluate the pavement performance of GTR-modified and polymer-modified asphalt mixtures. To reveal the strain and stress relationship under different frequencies and temperatures, the dynamic modulus test was applied. The Hamburg wheel tracking device (HWTD) was used to assess the high-temperature deformation resistance. The disc-shaped compact tension (DCT) test was used to evaluate the low-temperature cracking characteristics. The characteristics of the asphalt binder were assessed by the dynamic shear rheometer (DSR) for high-temperature properties and the asphalt binder cracking device (ABCD) for low-temperature properties. After the construction, a field noise test was conducted. The experimental results stated that the polymer-modified asphalt mixture and GTR-modified asphalt mixture showed higher dynamic modulus and better ability to prevent cracking than the conventional asphalt mixture at low temperatures, as well as better permanent deformation and stripping resistance than the conventional asphalt mixture. The fracture energy of the GTR-modified hot mix asphalt (HMA) is 13–16 % larger than the polymer-modified HMA. The number of passes to the stripping point of GTR-modified was 510–518 % higher than the conventional HMA. When compared to the field core, the lab-compacted HMA offers superior pavement performance. The extracted asphalt binder test results show the GTR-modified asphalt has better rutting resistance and cracking resistance than polymer-modified asphalt, and the results in the noise test demonstrated that the rubber-modified asphalt pavement mitigated the noise level by 2–3 dB on the road at different vehicle speeds. Moreover, the pavement condition was noticeably enhanced after the reconstruction of the surface course. The total number of passenger tires to be used in this project is about 2270. To summarize, better rutting and cracking properties in asphalt pavement are shown by the project\u27s utilization of rubber technology. And the GTR-modified HMA is comparable to polymer-modified HMA. Therefore, it may be appropriate to utilize rubber technology on high-traffic volume asphalt pavement in Michigan\u27s wet and freeze climate

Acute glycogen synthase kinase-3 inhibition modulates human cardiac conduction

Glycogen synthase kinase 3 (GSK-3) inhibition has emerged as a potential therapeutic target for several diseases, including cancer. However, the role for GSK-3 regulation of human cardiac electrophysiology remains ill-defined. We demonstrate that SB216763, a GSK-3 inhibitor, can acutely reduce conduction velocity in human cardiac slices. Combined computational modeling and experimental approaches provided mechanistic insight into GSK-3 inhibition-mediated changes, revealing that decreased sodium-channel conductance and tissue conductivity may underlie the observed phenotypes. Our study demonstrates that GSK-3 inhibition in human myocardium alters electrophysiology and may predispose to an arrhythmogenic substrate; therefore, monitoring for adverse arrhythmogenic events could be considered

Chamber-specific transcriptional responses in atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, yet the molecular signature of the vulnerable atrial substrate is not well understood. Here, we delineated a distinct transcriptional signature in right versus left atrial cardiomyocytes (CMs) at baseline and identified chamber-specific gene expression changes in patients with a history of AF in the setting of end-stage heart failure (AF+HF) that are not present in heart failure alone (HF). We observed that human left atrial (LA) CMs exhibited Notch pathway activation and increased ploidy in AF+HF but not in HF alone. Transient activation of Notch signaling within adult CMs in a murine genetic model is sufficient to increase ploidy in both atrial chambers. Notch activation within LA CMs generated a transcriptomic fingerprint resembling AF, with dysregulation of transcription factor and ion channel genes, including Pitx2, Tbx5, Kcnh2, Kcnq1, and Kcnip2. Notch activation also produced distinct cellular electrophysiologic responses in LA versus right atrial CMs, prolonging the action potential duration (APD) without altering the upstroke velocity in the left atrium and reducing the maximal upstroke velocity without altering the APD in the right atrium. Our results support a shared human/murine model of increased Notch pathway activity predisposing to AF

Color-Stable Blue Light-Emitting Diodes Enabled by Effective Passivation of Mixed Halide Perovskites

Bandgap tuning through mixing halide anions is one of the most attractive features for metal halide perovskites. However, mixed halide perovskites usually suffer from phase segregation under electrical biases. Herein, we obtain high-performance and color-stable blue perovskite LEDs (PeLEDs) based on mixed bromide/ chloride three-dimensional (3D) structures. We demonstrate that the color instability of CsPb(Br1-xClx)(3) PeLEDs results from surface defects at perovskite grain boundaries. By effective defect passivation, we achieve color-stable blue electroluminescence from CsPb(Br1-xClx)(3) PeLEDs, with maximum external quantum efficiencies of up to 4.5% and high luminance of up to 5351 cd m(-2) in the sky-blue region (489 nm). Our work provides new insights into the color instability issue of mixed halide perovskites and can spur new development of high-performance and color-stable blue PeLEDs.Funding Agencies|ERC Starting GrantEuropean Research Council (ERC) [717026]; Swedish Energy Agency EnergimyndighetenSwedish Energy Agency [48758-1, 44651-1]; Swedish Foundation for International Cooperation in Research and Higher Education [CH2018-7736]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [200900971]; China Scholarship CouncilChina Scholarship Council</p

Endothelial Cell Selectivity to Nanoparticles Depends on Mechanical Phenotype

Abstract Endothelial cells (ECs) elongate in the direction of blood flow, are stiffer, and are considered atheroprotective in areas of the vasculature where flow‐induced shear stress is high and unidirectional and are softer, atherogenic, and polygonal in areas experiencing oscillatory multidirectional flow. To understand the precise roles of EC mechanics and morphology in the uptake of therapeutic nanoparticles (NPs) by atherogenic endothelium, human aortic ECs are induced to adopt prescribed shapes and areas imposed by microcontact patterned adhesive islands. NP uptake per cell increases with increasing spreading area and decreases with increasing cell aspect ratio at constant cell spreading area. Biomechanical analysis shows that elongated cells exhibit higher cellular stress and stiffer membranes than cells with low aspect ratios, indicating a strong correlation between morphology, mechanical phenotype, and NP uptake. Further, ECs elongated by high laminar shear endocytosed NPs to a far lesser extent than those that are nonelongated in the chaotic, lower shear areas when cocultured in the same chamber. Results indicate that conditions leading to atherogenesis, such as low, chaotic shear‐induction of EC polygonal morphology may be used to increase the uptake of therapeutic NPs as a preventative measure against atherosclerosis