If A method of studying the design variables pertinent to agitated gas-liquid reactors has been developed; the catalyzed rate of air oxidation of aqueous sodium sulfite and the agitator power consumption are measured. Volumetric absorption coefficients for agitated contactors are shown to vary with (agitator power)0•95 and with (gas velocity)0•67, giving rise to a new function, absorption number, defined as /Cy/V,0•67, where KY is the absorption coefficient and Vs is the average gas velocity based on the cross section of the reactor. When plotted against,agitator power input per unit volume of liquid, this function is shown to correlate data for vaned-disk impellers and flat paddles covering, respectively, threeand tenfold variations of scale size,• it thus becomes a satisfactory basis for the design of plant equipment. Power magnitudes ranging from 10 to 3000 ft.-lb./(min.Xcu.ft.) and gas rates ranging from 20 to 360 feet/hour are reported. Application of this correlation to the study of design variables is illustrated by data relating the performance of a laboratory reactor to liquid depth. A no-gas power correlation of the familiar power function-Reynolds number type is presented for the vaned disk operating in a baffled tank. FOR absorption applications to which conventional plate or packed columns are not well suited, such as gas-liquid reac-65

Plasma carboxypeptidase B (PCB) is an exopeptidase that exerts an antifibrinolytic effect by releasing C-terminal Lys and Arg residues from partially degraded fibrin. PCB is produced in plasma via limited proteolysis of the zymogen, pro-PCB. In this report, we show that the K m (55 nM) for plasmin-catalyzed activation of pro-PCB is similar to the plasma concentration of pro-PCB (50 -70 nM), whereas the K m for the thrombin-or thrombin:thrombomodulin-catalyzed reaction is 10 -40-fold higher than the pro-PCB level in plasma. Additionally, tissue-type plasminogen activator triggers activation of pro-PCB in blood plasma in a reaction that is stimulated by a neutralizing antibody versus ␣ 2 -antiplasmin. Together, these results show that plasmin-mediated activation of pro-PCB can occur in blood plasma. Heparin (UH) and other anionic glycosaminoglycans stimulate pro-PCB activation by plasmin but not by thrombin or thrombin:thrombomodulin. Pro-PCB is a more favorable substrate for plasmin in the presence of UH (16-fold increase in k cat /K m ). UH also stabilizes PCB against spontaneous inactivation. The presence of UH in clots prepared with prothrombin-deficient plasma delays tissue-type plasminogen activator-triggered lysis; this effect of UH on clot lysis is blocked by a PCB inhibitor from potato tubers. These results show that UH accelerates plasmin-catalyzed activation of pro-PCB in plasma and PCB, in turn, stabilizes fibrin against fibrinolysis. We propose that glycosaminoglycans in the subendothelial extracellular matrix serve to augment the levels of PCB activity thereby stabilizing blood clots at sites where there is a breach in the integrity of the vasculature.

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.

Alongside the rising global water demand, continued stress on current water supplies has sparked interest in using nontraditional source waters for energy, agriculture, industry, and domestic needs. Membrane technologies have emerged as one of the most promising approaches to achieve water security, but implementation of membrane processes for increasingly complex waters remains a challenge. The technical feasibility of membrane processes replacing conventional treatment of alternative water supplies (e.g., wastewater, seawater, and produced water) is considered in the context of typical and emerging water quality goals. This review considers the effectiveness of current technologies (both conventional and membrane based), as well as the potential for recent advancements in membrane research to achieve these water quality goals. We envision the future of water treatment to integrate advanced membranes (e.g., mixed-matrix membranes, block copolymers) into smart treatment trains that achieve several goals, including fit-for-purpose water generation, resource recovery, and energy conservation.

We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.