Conceptual Design of an In-Space Cryogenic Fluid Management Facility

The conceptual design of a Spacelab experiment to develop the technology associated with low gravity propellant management is presented. The proposed facility consisting of a supply tank, receiver tank, pressurization system, instrumentation, and supporting hardware, is described. The experimental objectives, the receiver tank to be modeled, and constraints imposed on the design by the space shuttle, Spacelab, and scaling requirements, are described. The conceptual design, including the general configurations, flow schematics, insulation systems, instrumentation requirements, and internal tank configurations for the supply tank and the receiver tank, is described. Thermal, structural, fluid, and safety and reliability aspects of the facility are analyzed. The facility development plan, including schedule and cost estimates for the facility, is presented. A program work breakdown structure and master program schedule for a seven year program are included

Conceptual design of an in-space cryogenic fluid management facility, executive summary

The conceptual design of a Spacelab experiment to develop the technology associated with low gravity propellant management is summarized. The preliminary facility definition, conceptual design and design analysis, and facility development plan, including schedule and cost estimates for the facility, are presented

Miniature reciprocating heat pumps and engines

The present invention discloses a miniature thermodynamic device that can be constructed using standard micro-fabrication techniques. The device can be used to provide cooling, generate power, compress gases, pump fluids and reduce pressure below ambient (operate as a vacuum pump). Embodiments of the invention relating to the production of a cooling effect and the generation of electrical power, change the thermodynamic state of the system by extracting energy from a pressurized fluid. Energy extraction is attained using an expansion process, which is as nearly isentropic as possible for the appropriately chosen fluid. An isentropic expansion occurs when a compressed gas does work to expand, and in the disclosed embodiments, the gas does work by overcoming either an electrostatic or a magnetic force

Cooling Scheme for BNL-Built LHC Magnets

Brookhaven National Laboratory (BNL) will provide four types of magnets, identified as D1, D2, D3 and D4, for the Insertion Regions of the Large Hadron Collider (LHC) as part of an international collaboration. These magnets utilize the dipole coil design of the Relativistic Heavy Ion Collider (RHIC) at BNL, for performance, reliability and cost reasons. The magnet cold mass and cryostat have been designed to ensure that these magnets meet all performance requirements in the LHC sloped tunnel using its cryogenic distribution system. D1 is a RHIC arc dipole magnet. D2 and D4 are 2-in-1 magnets, two coils in one cold mass, in a cryostat. D3 is a 1-in-1 magnet, one coil in one cold mass, with two cold masses side by side in a cryostat. D1 and D4 will be cooled by helium II at 1.9 K using a bayonet heat exchanger similar to the main cooling system of LHC. D2 and D3 will be cooled by liquid helium at 4.5 K using a Two-Feed scheme. A detailed description of the cooling scheme for these magnets, their cryostats, special features and interfaces with the LHC distribution system is given

No interactions between heparin and atacicept, an antagonist of B cell survival cytokines.

The TNF family ligands, B cell activating factor of the TNF family (BAFF, also known as B lymphocyte stimulator, BLyS) and a proliferation-inducing ligand (APRIL), share the transmembrane activator and calcium-modulator and cyclophilin ligand (CAML)-interactor (TACI) as one of their common receptors. Atacicept, a chimeric recombinant TACI/IgG1-Fc fusion protein, inhibits both ligands. TACI and APRIL also bind to proteoglycans and to heparin that is structurally related to proteoglycans. It is unknown whether the portion of TACI contained in atacicept can bind directly to proteoglycans, or indirectly via APRIL, and whether this could interfere with the anti-coagulant properties of heparin. Binding of atacicept and APRIL to proteoglycan-positive cells was measured by FACS. Activities of heparin and atacicept were measured with activated factor Xa inhibition and cell-based assays. Effects of heparin on circulating atacicept was monitored in mice. Atacicept did not bind to proteoglycan-positive cells, but when complexed to APRIL could do so indirectly via APRIL. Multimers of atacicept obtained after exposure to cysteine or BAFF 60-mer bound directly to proteoglycans. Atacicept alone, or in complex with APRIL, or in a multimeric form did not interfere with heparin activity in vitro. Conversely, heparin did not influence inhibition of BAFF and APRIL by atacicept and did not change circulating levels of atacicept. Lack of detectable interference of APRIL-bound or free atacicept on heparin activity makes it unlikely that atacicept at therapeutic doses will interfere with the function of heparin in vivo

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated

Characterization and application of two RANK-specific antibodies with different biological activities.

Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-κB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-κB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools

BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid.

B cell activation factor of the TNF family (BAFF/BLyS), an essential B cell survival factor of which circulating levels are elevated in several autoimmune disorders, is targeted in the clinic for the treatment of systemic lupus erythematosus (SLE). The soluble form of BAFF can exist as 3-mer, or as 60-mer that results from the ordered assembly of twenty 3-mers and that can be obtained from naturally cleaved membrane-bound BAFF or made as a recombinant protein. However, which forms of soluble BAFF exist and act in humans is unclear. In this study, BAFF 3-mer and 60-mer in biological fluids were characterized for size, activity and response to specific stimulators or inhibitors of BAFF. Human cerebrospinal fluids (CSF) from patients with multiple sclerosis and adult human sera contained exclusively BAFF 3-mer in these assays, also when BAFF concentrations were moderately SLE or highly (BAFFR-deficient individual) increased. Human sera, but not CSF, contained a high molecular weight, saturable activity that dissociated preformed recombinant BAFF 60-mer into 3-mer. This activity was lower in cord blood. Cord blood displayed BAFF levels 10-fold higher than in adults and consistently contained a fair proportion of active high molecular weight BAFF able to dissociate into 3-mer but not endowed with all properties of recombinant BAFF 60-mer. If BAFF 60-mer is produced in humans, it is dissociated, or at least attenuated in the circulation