ABSTRACT
Separate biological elimination of nitrogen from the digester supernatant of a municipal wastewater treatment plant (WWTP) was investigated in pilot and full-scale plants. Denitrification mainly via nitrite was achieved in a sequencing batch reactor (SBR) and a continuous flow reactor (CSTR or SHARON). Suppression of nitrite oxidation in the SBR was feasible at short aerobic/anaerobic intervals allowing for immediate denitrification of the produced nitrite. Nitrate production could also be stopped by exposing the biomass to anaerobic conditions for 11 days. Temporarily high concentrations (up to 80 gNH3-Nm(-3)) of free ammonia could not be considered as the major reason for inhibiting nitrite oxidation. In a full-scale SBR plant 90% of the nitrogen load was denitrified in a total hydraulic retention time (HRT) of 1.6 days and with a sludge age between 15 and 20 days. Ethanol and methanol were used for denitrification. The specific average substrate consumption was 2.2 gCOD(dosed) g(-1)N(removed) with an effective biomass yield of 0.2 gCOD(biomass) g(-1)COD(dosed). No dosing with base was required. In the SHARON process full nitrogen elimination was achieved only with a total HRT greater than 4 days at 29 degrees C. The overall costs were estimated at 1.4 euros kg(-1)N(removed) for the SBR and 1.63 euros kg(-1)N(removed) in SHARON mode, respectively. The SHARON process is simple in operation (CSTR) but the tank volume has to be significantly greater than in SBR.
Subject(s)
Bioreactors , Nitrogen/isolation & purification , Waste Disposal, Fluid/methods , Water Purification/methods , Bacteria, Aerobic , Bacteria, Anaerobic , Cities , Water MovementsABSTRACT
The dependence of K+ production on the nuclear equation of state is investigated in heavy-ion collisions. An increase of the excitation function of K+ multiplicities obtained in heavy (Au+Au) over light (C+C) systems when going far below threshold which has been observed by the KaoS Collaboration strongly favors a soft equation of state. This observation holds despite the influence of an in-medium kaon potential predicted by effective chiral models which is necessary to reproduce the experimental K+ yields.
ABSTRACT
Based on X-ray crystal structure information, mono charged phosphinate isosteres of phosphotyrosine have been designed and incorporated in a short inhibitory peptide sequence of the Grb2-SH2 domain. The resulting compounds, by exploiting additional interactions, inhibit binding to the Grb2-SH2 domain as potently as the corresponding doubly charged (phosphonomethyl)phenylalanine analogue.
Subject(s)
Adaptor Proteins, Signal Transducing , Oligopeptides/chemical synthesis , Phosphinic Acids/chemical synthesis , Phosphotyrosine/analogs & derivatives , Phosphotyrosine/chemical synthesis , Proteins/antagonists & inhibitors , Proteins/chemistry , Binding Sites , Crystallography, X-Ray , Drug Design , GRB2 Adaptor Protein , Hydrogen Bonding , Ligands , Oligopeptides/chemistry , Oligopeptides/pharmacology , Phosphinic Acids/chemistry , Phosphinic Acids/pharmacology , Phosphotyrosine/chemistry , Structure-Activity Relationship , src Homology DomainsABSTRACT
A series of novel phosphinates, derived from 4-phosphonomethylphenylalanine, are described as isosteres of phosphotyrosine. Benzyl (or alkyl) phosphinomethylphenylalanine derivatives were prepared by alkylation of an amino acid P-H phosphinate.
Subject(s)
Adaptor Proteins, Signal Transducing , Phenylalanine/analogs & derivatives , Phosphinic Acids/chemical synthesis , Phosphotyrosine/analogs & derivatives , Proteins/antagonists & inhibitors , Proteins/chemistry , Amino Acids , Drug Design , GRB2 Adaptor Protein , Molecular Structure , Phosphinic Acids/chemistry , Phosphinic Acids/pharmacology , Phosphotyrosine/chemical synthesis , Phosphotyrosine/chemistry , Structure-Activity Relationship , src Homology DomainsABSTRACT
CGP 53437 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease containing a hydroxyethylene isostere. The compound inhibited recombinant HIV-1 protease with a Ki of 0.2 nM. The inhibition constant versus human cathepsin D and human cathepsin E was 4 nM. Human pepsin and gastricsin were inhibited with Kis of 8 and 500 nM, respectively, and human renin was inhibited with a Ki of 190 microM. The replication of HIV-1/LAV, HIV-1/Z-84, and HIV-1/pLAI was inhibited with a 90% effective dose of 0.1 microM in acutely infected MT-2 cells. The 50% cytotoxic dose was 100 microM. Similar antiviral activity was observed when the compound was added up to 10 h after infection. At the effective concentration, processing of Gag precursor protein p55 was greatly reduced, confirming an action on the late stage of the virus life cycle, as expected. The efficacy of the inhibitor was also demonstrated by using primary human peripheral blood lymphocytes infected with the HIV-1/LAV strain, low-passage clinical isolates obtained from HIV-1-seropositive individuals (including a zidovudine-resistant strain), and HIV-2/ROD. In these cells, CGP 53437 delayed the onset of HIV replication in a dose-dependent fashion (substantial effects with concentrations of > or = 0.1 microM) as long as the inhibitor was maintained in the culture. CGP 53437 was orally bioavailable in mice. Concentrations in plasma 10-fold in excess of the in vitro antiviral 90% effective dose could be sustained for several hours after oral application of 120 mg/kg. Therefore, CGP 53437 has the potential to be a therapeutically useful anti-HIV agent for the treatment of AIDS.