HFE and transferrin directly compete for transferrin receptor in solution and at the cell surface

Transferrin receptor (TfR) is a dimeric cell surface protein that binds both the serum iron transport protein transferrin (Fe-Tf) and HFE, the protein mutated in patients with the iron overload disorder hereditary hemochromatosis. HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, but HFE binding to TfR lowers the apparent affinity of the Fe-Tf/TfR interaction. This apparent affinity reduction could result from direct competition between HFE and Fe-Tf for their overlapping binding sites on each TfR polypeptide chain, from negative cooperativity, or from a combination of both. To explore the mechanism of the affinity reduction, we constructed a heterodimeric TfR that contains mutations such that one TfR chain binds only HFE and the other binds only Fe-Tf. Binding studies using a heterodimeric form of soluble TfR demonstrate that TfR does not exhibit cooperativity in heterotropic ligand binding, suggesting that some or all of the effects of HFE on iron homeostasis result from competition with Fe-Tf for TfR binding. Experiments using transfected cell lines demonstrate a physiological role for this competition in altering HFE trafficking patterns

Advanced mission analysis programs

Computer programs provide preliminary trajectory and guidance information required for feasibility studies in space mission analysis. The advanced mission analysis computer programs include programs for approximate solutions, programs for targeting and output, and programs for Monte Carlo and linear guidance analysis

Few and Far Between: How HIV May Be Evading Antibody Avidity

No abstract

Flight test results of the Strapdown hexad Inertial Reference Unit (SIRU). Volume 3: Appendices A-G

Results of flight tests of the Strapdown Inertial Reference Unit (SIRU) navigation system are presented. The fault tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance. Selected facets of the flight tests are also described in detail and include some of the following: (1) flight test plans and ground track plots; (2) navigation residual plots; (3) effects of approximations in navigation algorithms; (4) vibration spectrum of the CV-340 aircraft; and (5) modification of the statistical FDICR algorithm parameters for the flight environment

Flight test results of the strapdown hexad inertial reference unit (SIRU). Volume 2: Test report

Results of flight tests of the Strapdown Inertial Reference Unit (SIRU) navigation system are presented. The fault tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance. Performance shortcomings are analyzed