Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thermal consequences of coal utilization are most meaningfully assessed in comparison with the form of power generation replaced by coal which is most likely nuclear. The different effects are influenced by siting decisions and the intrinsic thermal efficiencies of the two fuel systems. Nuclear power plants discharge 50% more waste Rheat to the atmosphere through cooling towers or to a water body than coal-fired plants. Coal-fired plants require about 2/3 as much water as nuclear power plants. Nearly every property of water is affected nonlinearly by temperature, and biological effects may amplify these changes because protein denaturation takes place more rapidly above 30 degrees C and these high temperatures affect bactericidal and viricidal activity of chlorine compounds. Usually algal populations change from a dominance of diatoms and green algae to dominance by blue-green algae. All organisms experience elevated metabolic rates at higher temperatures which may affect total energy needs, foraging ability, reproduction, migration and susceptibility to disease. Intake structures inevitably draw many organisms into the cooling system of a power plant, but the number and kind are influenced by its location, configuration, and mode of operation. Use of water recirculation systems reduces water use and with it, the number of organisms entrained. Mechanical damage in the cooling system to small organisms is generally low, but fish and their larvae and eggs may be seriously damaged. Discharge effects may also be severe but are generally local. The near field, where there are strong shear velocities and rapid temperature changes are particularly stressful to fish, and stringent limitations on the timing and strength of discharges may be required to reduce these stresses to nondamaging levels. Off-stream cooling systems may increase cloudiness, ground fog, precipitation, temperature and local winds, but these effects generally extend no further than 1000 m even in winter. There is considerable potential for using condenser cooling water for agricultural and aquacultural purposes such as irrigation, frost protection, undersoil heating, greenhouse heating and climate control. However, over the next few decades little of this waste heat is likely to be used creatively. The thermal consequences of implementing NEP are locally serious but do not pose regional problems. Creative use of the waste heat for aquaculture, agriculture, cogeneration, and power for energy intensive industries can be a powerful means of mitigating undesirable effects.
 ...
PMID:Thermal pollution consequences of the implementation of the president's energy message on increased coal utilization. 54 Jun 23

Inhibition of neprilysin (NEP) is widely studied as a therapeutic target for the treatment of hypertension, heart failure, and kidney disease. Sacubitril/valsartan (LCZ696) is a drug approved to reduce the risk of cardiovascular death in heart failure patients with reduced ejection fraction. LBQ657 is the active metabolite of sacubitril and an inhibitor of NEP. Previously, we have reported the crystal structure of NEP bound with LBQ657, whereby we noted the presence of a subsite in S1' that has not been explored before. We were also intrigued by the zinc coordination made by one of the carboxylic acids of LBQ657, leading us to explore alternative linkers to efficiently engage zinc for NEP inhibition. Structure-guided design culminated in the synthesis of selective, orally bioavailable, and subnanomolar inhibitors of NEP. A 17-fold boost in biochemical potency was observed upon addition of a chlorine atom that occupied the newly found subsite in S1'. We report herein the discovery and preclinical profiling of compound 13, which paved the path to our clinical candidate.
 ...
PMID:Structure-Guided Design of Substituted Biphenyl Butanoic Acid Derivatives as Neprilysin Inhibitors. 3207 87