Differential Roles for the Coagulation Factors XI and XII in Regulating the Physical Biology of Fibrin.

In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation. Fibrin formation was initiated with tissue factor, ellagic acid (EA), or LC polyP in the presence of inhibitors of FXI and FXII. Our data demonstrated that inhibition of FXI decreased the rate of fibrin formation and fiber network density, and increased the fibrin network strength and rate of fibrinolysis when gelation was initiated via the contact activation pathway with EA. FXII inhibition decreased the fibrin formation and fibrin density, and increased the fibrinolysis rate only when fibrin formation was initiated via the contact activation pathway with LC polyP. Overall, we demonstrate that inhibition of FXI and FXII distinctly alter the biophysical properties of fibrin.

Ammonia loading rate: an effective variable to control partial nitrification and generate the anaerobic ammonium oxidation influent.

Anaerobic ammonium oxidation (ANAMMOX) is an innovative process for the treatment of ammonia-contaminated waters. ANNAMOX is usually preceded by a nitrifying step in which ammonia is partially oxidized to nitrite. The effectiveness of the overall process depends on control of the nitrification and creation of a suitable influent for ANAMMOX. In this work, impacts of ammonia concentration and loading rate on partial nitrification and composition of the resulting effluent were investigated in continuous stirred tank (CSTR) and biofilm reactors fed with various ammonia concentrations (17.6-61.5 mM; 299-1045 ppm). Regardless of ammonia concentration, loading rates from 3.1 to 5.4mM/h in the CSTR and 6.4-12.1 mM/h in the biofilm reactor generated effluents with nitrite to ammonia ratios of 1.2 +/- 0.3 (suitable ANAMMOX influent). Under these conditions, the highest ammonia loading and nitrite production rates in the CSTR and biofilm reactors were 5.4 and 2.5 mM/h (HRT: 3.7 h) and 12.1 and 6.5 mM/h (HRT: 1.6 h), respectively. Results reveal that ammonia loading rate can be used effectively to achieve suitable ANAMMOX influent without the need for precise control of dissolved oxygen (DO). Considering the difficulty in regulating DO in large-scale systems and the need for the nitrifying process to be flexible with respect to various ammonia concentrations, the loading rate appears to be a practical option to control partial nitrification. Verifying the range of ammonia loading rates that generate ANAMMOX influent allows operation of the nitrifying step with any level of ammonia in the feed, with the proper loading rate achieved through adjustment of hydraulic residence time.