Long-term durability testing of ceramic cross-flow filter. Final report, September 29, 1987--December 31, 1992

Long term durability testing of the cross flow filter is described. Two high temperature, high pressure test facilities were built and operated. The facilities were designed to simulate dirty gas environments typical of Pressurized Fluidized Bed Combustion (PFBC) and coal gasification. Details of the design and operation of the test facilities and filter testing results are described

Use of Activity-Based Probes to Develop High Throughput Screening Assays That Can Be Performed in Complex Cell Extracts

Background: High throughput screening (HTS) is one of the primary tools used to identify novel enzyme inhibitors. However, its applicability is generally restricted to targets that can either be expressed recombinantly or purified in large quantities. Methodology and Principal Findings: Here, we described a method to use activity-based probes (ABPs) to identify substrates that are sufficiently selective to allow HTS in complex biological samples. Because ABPs label their target enzymes through the formation of a permanent covalent bond, we can correlate labeling of target enzymes in a complex mixture with inhibition of turnover of a substrate in that same mixture. Thus, substrate specificity can be determined and substrates with sufficiently high selectivity for HTS can be identified. In this study, we demonstrate this method by using an ABP for dipeptidyl aminopeptidases to identify (Pro-Arg)2-Rhodamine as a specific substrate for DPAP1 in Plasmodium falciparum lysates and Cathepsin C in rat liver extracts. We then used this substrate to develop highly sensitive HTS assays (Z’.0.8) that are suitable for use in screening large collections of small molecules (i.e.300,000) for inhibitors of these proteases. Finally, we demonstrate that it is possible to use broad-spectrum ABPs to identify target-specific substrates. Conclusions: We believe that this approach will have value for many enzymatic systems where access to large amounts o

PP2A ligand ITH12246 protects against memory impairment and focal cerebral ischemia in mice

ITH12246 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8] naphthyridine-3-carboxylate) is a 1,8-naphthyridine described to feature an interesting neuroprotective profile in in vitro models of Alzheimer's disease. These effects were proposed to be due in part to a regulatory action on protein phosphatase 2A inhibition, as it prevented binding of its inhibitor okadaic acid. We decided to investigate the pharmacological properties of ITH12246, evaluating its ability to counteract the memory impairment evoked by scopolamine, a muscarinic antagonist described to promote memory loss, as well as to reduce the infarct volume in mice suffering phototrombosis. Prior to conducting these experiments, we confirmed its in vitro neuroprotective activity against both oxidative stress and Ca2+ overload-derived excitotoxicity, using SH-SY5Y neuroblastoma cells and rat hippocampal slices. Using a predictive model of blood-brain barrier crossing, it seems that the passage of ITH12246 is not hindered. Its potential hepatotoxicity was observed only at very high concentrations, from 0.1 mM. ITH12246, at the concentration of 10 mg/kg i.p., was able to improve the memory index of mice treated with scopolamine, from 0.22 to 0.35, in a similar fashion to the well-known Alzheimer's disease drug galantamine 2.5 mg/kg. On the other hand, ITH12246, at the concentration of 2.5 mg/kg, reduced the phototrombosis-triggered infarct volume by 67%. In the same experimental conditions, 15 mg/kg melatonin, used as control standard, reduced the infarct volume by 30%. All of these findings allow us to consider ITH12246 as a new potential drug for the treatment of neurodegenerative diseases, which would act as a multifactorial neuroprotectant.Peer Reviewe

Integrated low emissions cleanup system for direct coal fueled turbines. Twenty-eighth quarterly report, July--September 1994

The United States Department of Energy, Morgantown Energy Research Center (DOE/METC), is sponsoring the development of advanced, coal-fueled turbine power plants such as pressurized fluid bed combustion and coal gasification combined cycles. A major technical challenge remaining for the development of the coal-fueled turbine is high-temperature gas cleaning to meet environmental standards for sulfur oxides and particulate emissions, as well as to provide acceptable turbine life. The Westinghouse Electric Corporation, Science & Technology Center, is evaluating Integrated Low Emissions Cleanup (ILEC) concepts that have been configured to meet this technical challenge. These ILEC concepts simultaneously control sulfur, particulate, and alkali contaminants in the high-pressure process gases. This document reports the status of a program in the twenty-seventh quarter to develop this ILEC technology

Integrated low emissions cleanup system for coal fueled turbines Phase III bench-scale testing and evaluation

The United States Department of Energy, Morgantown Energy Research Center (DOE/METC), is sponsoring the development of coal-fired turbine technologies such as Pressurized Fluidized Bed Combustion (PFBC), coal Gasification Combined Cycles (GCC), and Direct Coal-Fired Turbines (DCFT). A major technical development challenge remaining for coal-fired turbine systems is high-temperature gas cleaning to meet environmental emissions standards, as well as to ensure acceptable turbine life. The Westinghouse Electric Corporation, Science & Technology Center, has evaluated an Integrated Low Emissions Cleanup (ILEC) concept that has been configured to meet this technical challenge. This ceramic hot gas filter (HGF), ILEC concept controls particulate emissions, while simultaneously contributing to the control of sulfur and alkali vapor contaminants in high-temperature, high-pressure, fuel gases or combustion gases. This document reports on the results of Phase III of the ILEC evaluation program, the final phase of the program. In Phase III, a bench-scale ILEC facility has been tested to (1) confirm the feasibility of the ILEC concept, and (2) to resolve some major filter cake behavior issues identified in PFBC, HGF applications

Integrated low emissions cleanup system for direct coal fueled turbines (moving bed, fluid bed contactor/ceramic filter). Twenty-ninth quarterly status report, October--December 1994

The United States Department of Energy, Morgantown Energy Research Center (DOE/METC), is sponsoring the development of advanced, coal-fueled turbine power plants such as pressurized fluid bed combustion and coal gasification combined cycles. A major technical challenge remaining for the development of the coal-fueled turbine is high-temperature gas cleaning to meet environmental standards for sulfur oxides and particulate emissions, as well as to provide acceptable turbine life. The Westinghouse Electric Corporation, Science & Technology Center, is evaluating Integrated Low Emissions Cleanup (ILEC) concepts that have been configured to meet this technical challenge. These ILEC concepts simultaneously control sulfur, particulate, and alkali contaminants in the high-pressure process gases. This document reports the status of a program in the twenty-seventh quarter to develop this ILEC technology