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- Giordanetto, Fabrizio, et al.
(författare)
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Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1 H-indol-1-yl]pyridine-2-yl}propanoic Acid
- 2018
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society. - 1948-5875. ; 9:7, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE-/- murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.
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| 3. |
- Hooey, Lawrence, et al.
(författare)
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Role of ferrous raw materials in the energy efficiency of integrated steelmaking
- 2014
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Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 54:3, s. 596-604
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Tidskriftsartikel (refereegranskat)abstract
- The role of ferrous raw materials and iron ore agglomeration in energy consumption of integrated steelmaking has been evaluated using a system-wide model. Four steelplant cases were defined: typical European steelplant with sinterplant; Nordic steelplant with sinterplant; European steelplant with sinter:pellet ratio of 50%, and Nordic steelplant charging pellets and a small amount of briquettes. Energy consumption in the mining system were estimated from published statistics at 150 MJ/t for lump ore and sinter fines, 650 MJ/t for pellets made from magnetite and 1 050 MJ/t for pellets made from hematite. An integrated steelplant model including all major unit operations was used to calculate overall system energy consumption from iron ore mining to hot rolled coil. Adjustments were made accounting for energy benefit of ground granulated blast furnace slag in cement production, energy required for cement production required for briquetting, and excess BF and BOF gas producing electricity in a 32% efficient power plant. The system-wide net adjusted energy in the first three steeplant cases showed marginal improvement with use of high grade sinter fines and decrease of pellet/sinter ratio to 50% compared to typical European case. Nordic steelplant charging pellets and briquettes had a reduction in system-wide energy of 5% to 8% for charging pellets from hematite or magnetite respectively compared to the typical European steelplant charging sinter and pellets made from hematite ore. Replacement of sinter with pellets was mainly responsible for the improvement with smaller contributions from magnetite ore in pelletizing.
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