Human Performance of Novice Schedulers for Complex Spaceflight Operations Timelines.

OBJECTIVE: Investigate the effects of scheduling task complexity on human performance for novice schedulers creating spaceflight timelines. BACKGROUND: Future astronauts will be expected to self-schedule, yet will not be experts in creating timelines that meet the complex constraints inherent to spaceflight operations. METHOD: Conducted a within-subjects experiment to evaluate scheduling task performance in terms of scheduling efficiency, effectiveness, workload, and situation awareness while manipulating scheduling task complexity according to the number of constraints and type of constraints. RESULTS: Each participant (n = 15) completed a set of scheduling problems. Results showed main effects of the number of constraints and type of constraint on efficiency, effectiveness, and workload. Significant interactions were observed in situation awareness and workload for certain types of constraints. Results also suggest that a lower number of constraints may be manageable by novice schedulers when compared to scheduling activities without constraints. CONCLUSION: Results suggest that novice schedulers' performance decreases with a high number of constraints, and future scheduling aids may need to target a specific type of constraint. APPLICATION: Knowledge on the effect of scheduling task complexity will help design scheduling systems that will enable self-scheduling for future astronauts. It will also inform other domains that conduct complex scheduling, such as nursing and manufacturing.

AKAPs in lipid rafts are required for optimal antigen presentation by dendritic cells.

Dendritic cell (DC) maturation and antigen presentation are regulated by activation of protein kinase A (PKA) signaling pathways, through unknown mechanisms. We have recently shown that interfering with PKA signaling through the use of anchoring inhibitor peptides hinders antigen presentation and DC maturation. These experiments provide evidence that DC maturation and antigen presentation are regulated by A-kinase anchoring proteins (AKAPs). Herein, we determine that the presence of AKAPs and PKA in lipid rafts regulates antigen presentation. Using a combination of western blotting and immuno-cytochemistry, we illustrate the presence of AKAP149, AKAP79, Ezrin and the regulatory subunits of PKA in DC lipid rafts. Incubation of DCs with the type II anchoring inhibitor, AKAP-in silico (AKAP-IS), removes Ezrin and RII from the lipid raft without disrupting raft formation. Addition of a lipid raft disruptor, methyl-ß-cyclodextrin, blocks the efficacy of AKAP-IS, suggesting that the lipid raft must be intact for AKAP-IS to inhibit antigen presentation. Ezrin and AKAP79 are present in the lipid raft of stimulated KG1 cells, but Ezrin is not present in the lipid raft of unstimulated KG1 cells and AKAP79 levels are greatly diminished, suggesting that Ezrin and AKAP79 may be the key AKAPs responsible for regulating antigen presentation.

A-kinase anchoring in dendritic cells is required for antigen presentation.

BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology.