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

Risk and Performance Assessment of Generic Mission Architectures: Showcasing the Artemis Mission

A has initiated a strong push to return face. In this work, we astronaut assess performance and risk for proposed mission architectures using a new Mission Architecture Risk Assessment (MARA) tool. The MARA tool can produce statistics about the availability of components and overall performance of the mission considering potential failures of any of its components. In a Monte Carlo approach, the tool repeats the mission simulation multiple times while a random generator lets modules fail according to their failure rates. The results provide statistically meaningful insights into the overall performance of the chosen architecture. A given mission architecture can be freely replicated in the tool, with the mission timeline and basic characteristics of employed mission modules (habitats, rovers, power generation units, etc.) specified in a configuration file. Crucially, failure rates for each module need to be known or estimated. The tool performs an event-driven simulation of the mission and accounts for random failure events. Failed modules can be repaired, which takes crew time but restores operations. In addition to tracking individual modules, MARA can assess the availability of predefined functions throughout the mission. For instance, the function of resource collection would require a rover to collect the resources, a power generation unit to charge the rover, and a resource processing module. Together, the modules that are required for a given function are called a functional group. Similarly, we can assess how much crew time is available to achieve a mission benefit (e.g. research, building a base, etc) as opposed to spending crew time on repairs. Here we employ the method on the proposed NASA Artemis mission. Artemis aims to return United States astronauts to the lunar surface by 2024. Results provide insights into mission failure probabilities, up- and downtime for individual modules and crew-time resources spent on the repair of failed modules. The tool also allows us to tweak the mission architecture in order to find setups that produce more favorable mission performance. As such, the tool can be an aid in improving the mission architect abling cost-benefit analysis for mission improvement

Minnesota and the American Rule: The Recoverability of Attorneys’ Fees Following In Re Silicone Implant Insurance Coverage Litigation

In the United States, a successful litigant is generally not entitled to recover attorneys\u27 fees from the opposing party absent specific statutory or contractual authorization. This basic principle is commonly referred to as the American Rule. Minnesota recognized and adopted the American Rule roughly 125 years ago. A limited number of exceptions to this longstanding rule exist, but Minnesota courts have generally been reluctant to expand or add to these exceptions. In Minnesota, an exception to the American Rule exists for fees incurred in a declaratory action to establish insurance coverage but only if the insurer has breached its duty to defend. The Minnesota Supreme Court created this exception almost forty years ago, and there have been numerous attempts to expand it, including the recent attempt by 3M and its amicus allies, the Commissioner of Commerce and the Minnesota Trial Lawyers Association. The Minnesota Supreme Court rejected this most recent attempt to expand the Morrison exception to the American Rule in In re Silicone Implant Insurance Coverage Litigation and reaffirmed that attorneys\u27 fees are recoverable in a declaratory judgment action only when the insurer breaches its contract with the insured by refusing to defend. This article will outline the historical underpinnings of the American Rule and its development under Minnesota law. It will also analyze the Morrison exception and the import of the Minnesota Supreme Court\u27s adherence to the narrow exception to the American Rule it carved out roughly four decades ago

Space station integrated wall design and penetration damage control. Task 3: Theoretical analysis of penetration mechanics

The efforts to provide a penetration code called PEN4 version 10 is documented for calculation of projectile and target states for the impact of 2024-T3 aluminum, R sub B 90 1018 steel projectiles and icy meteoroids onto 2024-T3 aluminum plates at impact velocities from 0 to 16 km/s. PEN4 determines whether a plate is perforated by calculating the state of fragmentation of projectile and first plate. Depth of penetration into the second to n sup th plate by fragments resulting from first plate perforation is determined by multiple cratering. The results from applications are given

Diagnostics Of Disks Around Hot Stars

We discuss three different observational diagnostics related to disks around hot stars: absorption line determinations of rotational velocities of Be stars; polarization diagnostics of circumstellar disks; and X-ray line diagnostics of one specific magnetized hot star, theta(1) Ori C. Some common themes that emerge from these studies include (a) the benefits of having a specific physical model as a framework for interpreting diagnostic data; (b) the importance of combining several different types of observational diagnostics of the same objects; and (c) that while there is often the need to reinterpret traditional diagnostics in light of new theoretical advances, there are many new and powerful diagnostics that are, or will soon be, available for the study of disks around hot stars

Experimental investigation of crater growth dynamics

This work is a continuation of an ongoing program whose objective is to perform experiments and to develop scaling relationships for large-body impacts onto planetary surfaces. The centrifuge technique is used to provide experimental data for actual target materials of interest. With both power and gas guns mounted on the rotor arm, it is possible to match various dimensionless similarity parameters, which have been shown to govern the behavior of large-scale impacts. The development of the centrifuge technique has been poineered by the present investigators and is documented by numerous publications, the most recent of which are listed below. Understanding the dependence of crater size upon gravity has been shown to be key to the complete determination of the dynamic and kinematic behavior of crater formation as well as ejecta phenomena. Three unique time regimes in the formation of an impact crater have been identified

Model for the Interaction of T-cell Receptors with Peptide/MHC Complexes

The immune response against a viral infection is mediated by two different types of cells known as B and T lymphocytes. The receptor on the B cell is the well-characterized antibody molecule, which exists in a membrane-bound form and in a secreted form involved in the initiation of complement-mediated killing and the inactivation of viral particles by direct binding. The recognition molecule on T cells is the membrane-bound T-cell antigen receptor, which has specificity for a combination of foreign antigen with a molecule of the major histocompatibility complex (MHC), as first demonstrated by Zinkernagel and Doherty (1974). MHC proteins exist in two closely related forms called class I and class II MHC molecules, both of which are cell-surface glycoproteins that are highly polymorphic in the human population. In general, class II MHC molecules are involved in interactions with T-helper cells, which cooperate with B cells to make antibody