MFA13 (MFA 2013)

Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum, May 3-July 29, 2013. Contents include Introduction / Buzz Spector -- The collaborative turn : new models of thinking, making, and learning / Patricia Olynyk -- [Introduction] / David Schuman -- Lyndon Barrois, Jr. / Rickey Laurentiis -- Sarah Bernhardt -- Shifting Shanghais / Hsuan Ying Chen -- Serhii Chrucky / JaNae Contag -- JaNae Contag / Emily Hanson -- Carrie DeBacker / Gabriel Feldman -- Erin M. Duhigg -- José Garza / Serhii Chrucky -- Eric Gray / Ariel Lewis -- Meghan Allynn Johnson : to or towards / Blair Allyn Johnson -- Hoa Le / Maria Xia -- Christine Eunji Lee -- Lavar Munroe : the black superhero when everyone was looking for the scapegoat / Patrick Johnson -- Jon A. Orosco : architectonics / Rickey Laurentiis -- Michael Powell / Nicholas Tamarkin -- Bridget A. Purcell : welcome home / Andy Chen -- Malahat Qureshi -- Natalie Rodgers / Katie McGinnis -- Carla Fisher Schwartz / Jennifer Padgett -- Zak Smoker -- Laurencia Strauss / Maura Pellettieri -- Lili Yang -- Vivian Zapata -- Contributors -- About the Sam Fox School.https://openscholarship.wustl.edu/books/1004/thumbnail.jp

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Tuning innate immune activation by surface texturing of polymer microparticles: the role of shape in inflammasome activation

Polymeric microparticles have been widely investigated as platforms for delivery of drugs, vaccines, and imaging contrast agents and are increasingly used in a variety of clinical applications. Microparticles activate the inflammasome complex and induce the processing and secretion of IL-1beta, a key innate immune cytokine. Recent work suggests that although receptors are clearly important for particle phagocytosis, other physical characteristics, especially shape, play an important role in the way microparticles activate cells. We examined the role of particle surface texturing not only on uptake efficiency but also on the subsequent immune cell activation of the inflammasome. Using a method based on emulsion processing of amphiphilic block copolymers, we prepared microparticles with similar overall sizes and surface chemistries but having either smooth or highly microtextured surfaces. In vivo, textured (budding) particles induced more rapid neutrophil recruitment to the injection site. In vitro, budding particles were more readily phagocytosed than smooth particles and induced more lipid raft recruitment to the phagosome. Remarkably, budding particles also induced stronger IL-1beta secretion than smooth particles through activation of the NLRP3 inflammasome. These findings demonstrate a pronounced role of particle surface topography in immune cell activation, suggesting that shape is a major determinant of inflammasome activation

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes