Cell culture systems for studying the combined effects of matrix proteins and mechanical forces on the behavior of soft tissue cells have not been well developed. Here, we describe a new biomimetic cell culture system that allows for the study of mixtures of matrix proteins while controlling mechanical stiffness in a range that is physiological for soft tissues. This system consists of layer-by-layer (LbL)-assembled films of native matrix proteins atop mechanically tunable soft supports. We used hepatic stellate cells, which differentiate to myofibroblasts in liver fibrosis, for proof-of-concept studies. By culturing cells on collagen and lumican LbL-modified hydrogels, we demonstrate that this system is noncytotoxic and offers a valid control substrate, that the hydrogel determines the overall system mechanics, and that the addition of lumican to collagen influences the stellate cell phenotype. LbL-modified hydrogels offer the potential to study the influence of complex environmental factors on soft-tissue cells in culture.
1-(Piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one ( 1) is a privileged substructure found in >1000 unique CGRP receptor antagonists. Two practical and efficient syntheses of 1 are described from complementary starting materials. One route features a chemoselective reductive amination, while the second route utilizes a Pd-catalyzed amination using an ammonia surrogate to overcome an issue of poor selectivity.
The description and operation of a novel, hybrid spouted vessel/fixed bed filter system for the removal of arsenic from water are presented. The system utilizes zero-valent iron (ZVI) particles circulating in a spouted vessel that continuously generates active colloidal iron corrosion products via the “self-polishing” action between ZVI source particles rolling in the moving bed that forms on the conical bottom of the spouted vessel. This action also serves as a “surface renewal” mechanism for the particles that provides for maximum utilization of the ZVI material. (Results of batch experiments conducted to examine this mechanism are also presented.) The colloidal material produced in this fashion is continuously captured and concentrated in a fixed bed filter located within the spouted vessel reservoir wherein arsenic complexation occurs. It is demonstrated that this system is very effective for arsenic removal in the microgram per liter arsenic concentration (i.e., drinking water treatment) range, reducing 100 μg/L of arsenic to below detectable levels (≪10 μg/L) in less than an hour. A mechanistic analysis of arsenic behavior in the system is presented, identifying the principal components of the population of active colloidal material for arsenic removal that explains the experimental observations and working principles of the system. It is concluded that the apparent kinetic behavior of arsenic in systems where colloidal (i.e., micro/nano) iron corrosion products are dominant can be complex and may not be explained by simple first or zeroth order kinetics.
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