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An active learning approach to the study of US national security decision making decision making can be achieved through the use of an in-class role-playing simulation. This article considers the importance of solid foundations for simulation design: (1) simulation preparation should be linked to class materials and learning outcomes, but also stand on its own; and (2) success in mirroring reality requires a careful, even rigid, simulation structure. This article also provides a methodology for assessing the simulation's impact on two separate issues: (1) student knowledge of the national security interagency process (based on a knowledge quiz given three times during the semester); and (2) student perception of the difficulty of making of national security decisions (based on a questionnaire given three times during the semester). Students were assigned roles within the national security bureaucracy, and presented with a challenge--the possibility of large-scale Iranian intervention in the Syrian Civil War. The assessment of student knowledge is still a work in process, complicated by logistical factors. The assessment of student perceptions of difficulty of decision making, however, yielded interesting preliminary results that should be replicated to make any conclusions more robust: Students began the course with a perception that national security decision making is highly complicated and difficult. Following lectures and readings, the perception of difficulty decreased significantly. However, the simulation increased student perception of decision making difficulty close to its original level. These results suggest that simulations are important for capturing complexities within decision making that lectures alone cannot.

The nature of the binding interactions of human protein C (PC) with acidic phospholipid (PL) vesicles was investigated using a series of mutant proteins altered at amino acid sequence 5. The results showed that the hydrophobic nature of residue-5 strongly influence protein binding and binding stability of PC to PL.

The hydrophobic residues at the amino terminus of the gamma-carboxyglutamic acid-rich region of human protein C are required for phospholipid (PL) binding and other PL-based activities. Leusine residues at positions 5 and 8 are important, as substitutions in these residues bring about changes in binding activity and are probably required for correct orientation of the enzymes on the PL surface. Human protein C belongs to a family of blood coagulation proteins that require vitamin K for activity.

The main binding site of human coagulation factor IX at the bovine aortic endothelial cell receptor is situated among the amino-terminal 14 amino acids of its light chain. This binding quality can be completely transferred to protein C. The study confirms the technique of using strategically generated chimeric recombinant molecules to indicate the areas of proteins' functional properties. It also permits new coagulation proteins to be constructed that have others' properties.

The helical stacks (HS) of recombinant (r)-protein C (PC) and r-activated protein C (APC) are needed for the proper alignment of the active site of the enzyme with the cleavage site of the substrate. Human PC is the precursor of the serine protease APC and is activated by human coagulation factor II and inhibited by calcium ions. APC is an anticoagulant which can cleave peptide bonds. Mutations prepared with substitutions in the amino acids in the HS of PC indicate that the HS is more important than the amino acid sequence in the calcium ion dependent reactions.

The functional properties of individual gamma-carboxyglutamic acid (Gla) residues of human protein C (PC) and activated protein C (APC) are studied using site-directed mutagenesis. Ca2+- and phospholipid-dependent anticoagulant properties of PC and APC do not require Gla14 and Gla19. Ca2+ coordination is facilitated by a single carboxylate of the Gla6 residue which is a crucial Ca2+ binding site.

The properties of gamma-carboxyglutamic acid (Gla) containing activated protein C and chimeric human protein C are studied by substituting helical stack (HS) domains of protein C with human coagulation factor IX. Gla and HS domains of the proteins are influenced by calcium ions, with homologous properties detected in factor IX. The calcium sites located outside protein domains is independent of the native Gla/HC domains within the protein.

Mutants which have Gla residue of r-activated human protein C (APC) are altered to Asp (D) residues by the dependence activity of activated human protein on its carboxyglutamine residues. The Va inactivation assay factors are used in assays of prothrombinase system having purified plasma. The mutants (GlaD)r-APC and (Gla-D)r-APC have very low activity in all the assays.

An analysis of recombinant activated chimeric human protein C (PC) that has its growth factor-like regions replaced by those of the human coagulation factor IX, reveals that PC retains its primary PC zymogen characteristics despite the substitution. PC adopts its Ca2+-dependent configuration without particular dependence on its epidermal growth factor (EGF). APD's EGF factors possess components that form a part of APC's anticoagulant characteristics.