5-Hydroxytryptamine (5-HT) 2C receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT 2C full agonist. Lorcaserin bound to human and rat 5-HT 2C receptors with high affinity (K i ϭ 15 Ϯ 1 nM, 29 Ϯ 7 nM, respectively), and it was a full agonist for the human 5-HT 2C receptor in a functional inositol phosphate accumulation assay, with 18-and 104-fold selectivity over 5-HT 2A and 5-HT 2B receptors, respectively. Lorcaserin was also highly selective for human 5-HT 2C over other human 5-HT receptors (5-HT 1A , 5-HT 3 , 5-HT 4C , 5-HT5 5A , 5-HT 6 , and 5-HT 7 ), in addition to a panel of 67 other G protein-coupled receptors and ion channels. Lorcaserin did not compete for binding of ligands to serotonin, dopamine, and norepinephrine transporters, and it did not alter their function in vitro. Behavioral observations indicated that unlike the 5-HT 2A agonist (Ϯ)-1-(2,5-dimethoxy-4-phenyl)-2-aminopropane, lorcaserin did not induce behavioral changes indicative of functional 5-HT 2A agonist activity. Acutely, lorcaserin reduced food intake in rats, an effect that was reversed by pretreatment with the 5-HT 2C -selective antagonist 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl-carbamoyl]indoline (SB242,084) but not the 5-HT 2A antagonist (R)-(ϩ)-␣-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907), demonstrating mediation by the 5-HT 2C receptor. Chronic daily treatment with lorcaserin to rats maintained on a high fat diet produced dose-dependent reductions in food intake and body weight gain that were maintained during the 4-week study. Upon discontinuation, body weight returned to control levels. These data demonstrate lorcaserin to be a potent, selective, and efficacious agonist of the 5-HT 2C receptor, with potential for the treatment of obesity.Serotonin mediates its physiological effects through at least 14 different receptors. The serotonin 5-HT 2 receptor subfamily contains three distinct receptor subtypes, 5-HT 2A , 5-HT 2B , and 5-HT 2C , all of which share considerable sequence homology (Ͼ80% in transmembrane spanning regions) and activate common signaling pathways, including G q ␣-mediated stimulation of phospholipase-C, elevation of intracellular inositol phosphates, and elevation of intracellular calcium (Roth et al., 1998). Human 5-HT 2C receptors are predominately expressed in the CNS, and they are highly enriched in choroid plexus, prefrontal cortex, hippocampus, basal ganglia, and other brain regions associated with the control of mood, cognition, and appetite (Roth et al., 1998). Thus, 5-HT 2C receptors have been proposed as a therapeutic target for the treatment of CNS disorders, including epilepsy, obsessive compulsive disorder, Parkinson's disease, schizophrenia, depression and anxiety, sleep disorders, and drug abuse (Tecott et al
Conventional projector-based display systems are typically designed around precise and regular configurations of projectors and display surfaces. While this results in rendering simplicity and speed, it also means painstaking construction and ongoing maintenance. In previously published work, we introduced a vision of projector-based displays constructed from a collection of casually-arranged projectors and display surfaces.In this paper, we present flexible yet practical methods for realizing this vision, enabling low-cost mega-pixel display systems with large physical dimensions, higher resolution, or both. The techniques afford new opportunities to build personal 3D visualization systems in offices, conference rooms, theaters, or even your living room. As a demonstration of the simplicity and effectiveness of the methods that we continue to perfect, we show in the included video that a 10-year old child can construct and calibrate a two-camera, two-projector, head-tracked display system, all in about 15 minutes.
Single best exposure tone-mapped Standard HDR Our result Figure 1. An exposure stack taken at a sculpture garden. In the first row from left to right: single best exposure tone-mapped, standard HDR, and our result. Our result captures all the range of the scene while being free of ghosting. The second row shows the original exposures in the stack. AbstractThe contrast in real world scenes is often beyond what consumer cameras can capture. For these situations, High Dynamic Range (HDR) images can be generated by taking multiple exposures of the same scene. When fusing information from different images, however, the slightest change in the scene can generate artifacts which dramatically limit the potential of this solution. We present a technique capable of dealing with a large amount of movement in the scene: we find, in all the available exposures, patches consistent with a reference image previously selected from the stack. We generate the HDR image by averaging the radiance estimates of all such regions and we compensate for camera calibration errors by removing potential seams. We show that our method works even in cases when many moving objects cover large regions of the scene.
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