Precursor Space Station Freedom experiments

The NASA Office of Aeronautics and Space Technology uses the In-Space Technology Experiments Program (IN-STEP) as the primary management vehicle to pursue innovative and potentially high payoff space technology experiments. The purpose of this presentation is to provide an overview of the IN-STEP approach in developing precursor Space Station experiments; identify those experiments now in the program; review the key points of the IN-STEP 1992 Announcement of Opportunity; and describe the OAST in-space technology experiments development process

Technology for the Future: In-Space Technology Experiments Program, part 2

The purpose of the Office of Aeronautics and Space Technology (OAST) In-Space Technology Experiments Program In-STEP 1988 Workshop was to identify and prioritize technologies that are critical for future national space programs and require validation in the space environment, and review current NASA (In-Reach) and industry/ university (Out-Reach) experiments. A prioritized list of the critical technology needs was developed for the following eight disciplines: structures; environmental effects; power systems and thermal management; fluid management and propulsion systems; automation and robotics; sensors and information systems; in-space systems; and humans in space. This is part two of two parts and contains the critical technology presentations for the eight theme elements and a summary listing of critical space technology needs for each theme

Technology for the Future: In-Space Technology Experiments Program, part 1

The purpose of the Office of Aeronautics and Space Technology (OAST) In-Space Technology Experiment Program (In-STEP) 1988 Workshop was to identify and prioritize technologies that are critical for future national space programs and require validation in the space environment, and review current NASA (In-Reach) and industry/university (Out-Reach) experiments. A prioritized list of the critical technology needs was developed for the following eight disciplines: structures; environmental effects; power systems and thermal management; fluid management and propulsion systems; automation and robotics; sensors and information systems; in-space systems; and humans in space. This is part one of two parts and is the executive summary and experiment description. The executive summary portion contains keynote addresses, strategic planning information, and the critical technology needs summaries for each theme. The experiment description portion contains brief overviews of the objectives, technology needs and backgrounds, descriptions, and development schedules for current industry, university, and NASA space flight technology experiments

Closed Timelike Curves and Holography in Compact Plane Waves

We discuss plane wave backgrounds of string theory and their relation to Goedel-like universes. This involves a twisted compactification along the direction of propagation of the wave, which induces closed timelike curves. We show, however, that no such curves are geodesic. The particle geodesics and the preferred holographic screens we find are qualitatively different from those in the Goedel-like universes. Of the two types of preferred screen, only one is suited to dimensional reduction and/or T-duality, and this provides a ``holographic protection'' of chronology. The other type of screen, relevant to an observer localized in all directions, is constructed both for the compact and non-compact plane waves, a result of possible independent interest. We comment on the consistency of field theory in such spaces, in which there are closed timelike (and null) curves but no closed timelike (or null) geodesics.Comment: 21 pages, 3 figures, LaTe

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART

Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host: implications for exosome stability and biology

Extracellular vesicles (EVs) mediate communication between cells and organisms across all 3 kingdoms of life. Several reports have demonstrated that EVs can transfer molecules between phylogenetically diverse species and can be used by parasites to alter the properties of the host environment. Whilst the concept of vesicle secretion and uptake is broad reaching, the molecular composition of these complexes is expected to be diverse based on the physiology and environmental niche of different organisms. Exosomes are one class of EVs originally defined based on their endocytic origin, as these derive from multivesicular bodies that then fuse with the plasma membrane releasing them into the extracellular environment. The term exosome has also been used to describe any small EVs recovered by high-speed ultracentrifugation, irrespective of origin since this is not always well characterized. Here, we use comparative global lipidomic analysis to examine the composition of EVs, which we term exosomes, that are secreted by the gastrointestinal nematode, Heligmosomoides polygyrus, in relation to exosomes secreted by cells of its murine host. Ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS) analysis reveals a 9- to 62-fold enrichment of plasmalogens, as well as other classes of ether glycerophospholipids, along with a relative lack of cholesterol and sphingomyelin (SM) in the nematode exosomes compared with those secreted by murine cells. Biophysical analyses of the membrane dynamics of these exosomes demonstrate increased rigidity in those from the nematode, and parallel studies with synthetic vesicles support a role of plasmalogens in stabilizing the membrane structure. These results suggest that nematodes can maintain exosome membrane structure and integrity through increased plasmalogens, compensating for diminished levels of other lipids, including cholesterol and SM. This work also illuminates the prevalence of plasmalogens in some EVs, which has not been widely reported and could have implications for the biochemical or immunomodulatory properties of EVs. Further comparative analyses such as those described here will shed light on diversity in the molecular properties of EVs that enable them to function in cross-species communication

Revolutionary Aerospace Systems Concepts - Planning for the Future of Technology Investments

In January, 2000, the NASA Administrator gave the following directions to Langley: "We will create a new role for Langley as a leader for the assessment of revolutionary aerospace system concepts and architectures, and provide resources needed to assure technology breakthroughs will be there to support these advanced concepts. This is critical in determining how NASA can best invest its resources to enable future missions." The key objective of the RASC team is to look beyond current research and technology (R&T) programs and missions and evolutionary technology development approaches with a "top-down" perspective to explore possible new mission capabilities. The accomplishment of this objective will allow NASA to provide the ability to go anywhere, anytime - safely, and affordably- to meet its strategic goals for exploration, science, and commercialization. The RASC Team will seek to maximize the cross-Enterprise benefits of these revolutionary capabilities as it defines the revolutionary enabling technology areas and performance levels needed. The product of the RASC Team studies will be revolutionary systems concepts along with enabling technologies and payoffs in new mission capabilities, which these concepts can provide. These results will be delivered to the NASA Enterprises and the NASA Chief Technologist for use in planning revolutionary future NASA R&T program investments