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We are creating families of designer G protein-coupled receptors (GPCRs) to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs, called receptors activated solely by synthetic ligands (RASSLs), are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like(More)
Quiescent mouse embryonic C3H/10T1/2 cells are more resistant to different proapoptotic stimuli than are these cells in the exponential phase of growth. However, the exponentially growing 10T1/2 cells are resistant to inhibitors of RNA or protein synthesis, whereas quiescent cells die upon these treatments. Conditioned medium from quiescent 10T1/2 cells(More)
Osteoblasts are essential for maintaining bone mass, avoiding osteoporosis, and repairing injured bone. Activation of osteoblast G protein-coupled receptors (GPCRs), such as the parathyroid hormone receptor, can increase bone mass; however, the anabolic mechanisms are poorly understood. Here we use "Rs1," an engineered GPCR with constitutive G(s) signaling,(More)
PURPOSE A four-generation Chinese family with 13 members affected with autosomal dominant congenital posterior polar cataract was studied. The purpose of this study was to identify the disease-causing gene in the family and to validate that mutations in CRYAB, the alphaB-crystallin gene, cause the congenital cataract. METHODS Linkage analysis was(More)
Security informatics is an emerging field of study focusing on the development and evaluation of advanced information technologies and systems for national and homeland security-related applications. Spatio-temporal hotspot analysis is an important component of security informatics since location and time are two critical aspects of most security-related(More)
G protein-coupled receptors (GPCRs) signal through a limited number of G-protein pathways and play crucial roles in many biological processes. Studies of their in vivo functions have been hampered by the molecular and functional diversity of GPCRs and the paucity of ligands with specific signaling effects. To better compare the effects of activating(More)
Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal bones. We identified and characterized two five-generation Chinese families with SYM1. The two families share some similarities (e.g., osseous fusion of interphalangeal joints of the 2-4 fingers)(More)
Motivated by the importance of infectious disease informatics (IDI) and the challenges to IDI system development and data sharing, we design and implement BioPortal, a Web-based IDI system that integrates cross-jurisdictional data to support information sharing, analysis, and visualization in public health. In this paper, we discuss general challenges in(More)
The NS5A protein plays a critical role in the replication of HCV and has been the focus of numerous research efforts over the past few years. NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays, making them attractive components for inclusion in all oral combination regimens. Early work in the NS5A arena led to the(More)