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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 613 records · Page 34
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

An anti-PD-1–GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy

Costimulatory receptors such as glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR) play key roles in regulating the effector functions of T cells. In human clinical trials, however, GITR agonist antibodies have shown limited therapeutic effect, which may be due to suboptimal receptor clustering-mediated signaling. To overcome this potential limitation, a rational protein engineering approach is needed to optimize GITR agonist-based immunotherapies. Here we show a bispecific molecule consisting of an anti-PD-1 antibody fused with a multimeric GITR ligand (GITR-L) that induces PD-1-dependent and FcγR-independent GITR clustering, resulting in enhanced activation, proliferation and memory differentiation of primed antigen-specific GITR + PD-1 + T cells. The anti-PD-1–GITR-L bispecific is a PD-1-directed GITR-L construct that demonstrated dose-dependent, immunologically driven tumor growth inhibition in syngeneic, genetically engineered and xenograft humanized mouse tumor models, with a dose-dependent correlation between target saturation and Ki67 and TIGIT upregulation on memory T cells. Anti-PD-1–GITR-L thus represents a bispecific approach to directing GITR agonism for cancer immunotherapy.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1986

Controls, health assessment, and conditional monitoring for large, reusable, liquid rocket engines

Past and future progress in the performance of control systems for large, liquid rocket engines typified such as current state-of-the-art, the Shuttle Main Engine (SSME), is discussed. Details of the first decade of efforts, which culminates in the F-1 and J-2 Saturn engines control systems, are traced, noting problem modes and improvements which were implemented to realize the SSME. Future control system designs, to accommodate the requirements of operation of engines for a heavy lift launch vehicle, an orbital transfer vehicle and the aerospace plane, are summarized. Generic design upgrades needed include an expanded range of fault detection, maintenance as-needed instead of as-scheduled, reduced human involvement in engine operations, and increased control of internal engine states. Current NASA technology development programs aimed at meeting the future control system requirements are described.

Cikanek, H. A., III↗
DOE OSTI2016

Engineering a Cysteine-Free Form of Human Fibroblast Growth Factor-1 for “Second Generation” Therapeutic Application

Human fibroblast growth factor-1 (FGF-1) has broad therapeutic potential in regenerative medicine but has undesirable biophysical properties of low thermostability and 3 buried cysteine (Cys) residues (at positions 16, 83, and 117) that interact to promote irreversible protein unfolding under oxidizing conditions. Mutational substitution of such Cys residues eliminates reactive buried thiols but cannot be accomplished simultaneously at all 3 positions without also introducing further substantial instability. The mutational introduction of a novel Cys residue (Ala66Cys) that forms a stabilizing disulfide bond (i.e., cystine) with one of the extant Cys residues (Cys83) effectively eliminates one Cys while increasing overall stability. This increase in stability offsets the associated instability of remaining Cys substitution mutations and permits production of a Cys-free form of FGF-1 (Cys16Ser/Ala66Cys/Cys117Ala) with only minor overall instability. The addition of a further stabilizing mutation (Pro134Ala) creates a Cys-free FGF-1 mutant with essentially wild-type biophysical properties. The elimination of buried free thiols in FGF-1 can substantially increase the protein half-life in cell culture. In this work, we show that the effective cell survival/mitogenic functional activity of a fully Cys-free form is also substantially increased and is equivalent to wild-type FGF-1 formulated in the presence of heparin sulfate as a stabilizing agent. The results identify this Cys-free FGF-1 mutant as an advantageous “second generation” form of FGF-1 for therapeutic application.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Bifacial effects of engineering tumour cell-derived exosomes on human natural killer cells

Extracellular vesicles (EVs) are nano vesicular structures that are secreted by almost all kinds of cells. Exosomes are small EVs derived from endosomes, with a diameter between 30–100 nm. Tumour-derived exosomes carry many molecules and factors from tumour cells. These exosomes are recognized and taken up by immunocytes. However, tumour-derived exosomes can not only suppress immune cell functions but also help tumours escape immune surveillance in the tumour microenvironment. The present work investigated the effect of exosomes derived from genetical modified K562 cells (GMK cells), which express IL-15, IL-18 and 4-1BBL (TNFSF9) on their surface. The results showed that these GME exosomes, carrying IL-15, IL-18 and 4-1BBL proteins similar to their host cells, could activate NK cells, increase the cytotoxicity of NK cells on some tumour cells in a short treatment (4 h) and promote NK cells proliferation. However, with an extended treatment time (48 h), these exosomes could inhibite the cytotoxicity of NK cells by inhibiting activated receptor expression on NK cells. These results indicated the bifacial effects of GMK exosomes on NK cells, which will be helpful to explore the possibility of using transformed exosomes as an anti-tumour immune vaccine or a therapeutic tool in future.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1985

The use of analogs in the innovation process - A software engineering protocol analysis

A human information processing account of how experienced practitioners utilize analogs in the innovation process is presented. The protocols of several practitioners are collected and analyzed. The problem behavior graphs, knowledge elements utilized, and operator elements applied are described, and a descriptive model of the innovation process is assembled. Implications for a production system, deviations from other models of the innovation process, and extensions to other models of the analogy procedure are explored.

Silverman, B. G.↗
NASA NTRS1994

Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

Carter, Daniel C.↗
NASA NTRS2013

Composite Design and Manufacturing Development for Human Spacecrafts

The Structural Engineering Division at the NASA Johnson Space Center (JSC) has begun work on lightweight, multi‐functional pressurized composite structures. The first candidate vehicle for technology development is the Multi‐Mission Space Exploration Vehicle (MMSEV) cabin, known as the Gen 2B cabin, which has been built at JSC by the Robotics Division. Of the habitable MMSEV vehicle prototypes designed to date, this is the first one specifically analyzed and tested to hold internal pressure and the only one made out of composite materials. This design uses a laminate base with zoned reinforcement and external stringers, intended to demonstrate certain capabilities, and to prepare for the next cabin design, which will be a composite sandwich panel construction with multi‐functional capabilities. As part of this advanced development process, a number of new technologies were used to assist in the design and manufacturing process. One of the methods, new to JSC, was to build the Gen 2B cabin with Out of Autoclave technology to permit the creation of larger parts with fewer joints. An 8‐ply pre‐preg layup was constructed to form the cabin body. Prior to lay‐up, a design optimization software called FiberSIM was used to create each ply pattern. This software is integrated with Pro/Engineer to allow for customized draping of each fabric ply over the complex tool surface. Slits and darts are made in the software model to create an optimal design that maintains proper fiber placement and orientation. The flat pattern of each ply is then exported and sent to an automated cutting table where the patterns are cut out of graphite material. Additionally, to assist in lay‐up, a laser projection system (LPT) is used to project outlines of each ply directly onto the tool face for accurate fiber placement and ply build‐up. Finally, as part of the OoA process, a large oven was procured to post‐cure each part. After manufacturing complete, the cabin underwent modal and pressure testing (currently in progress at date of writing) and will go on to be outfitted and used for further ops usage.

Litteken, Douglas↗
NASA NTRS2004

Developing Advanced Support Technologies for Planetary Exploration Missions

The United States Vision for Space Exploration calls for sending robots and humans to explore the Earth s moon, the planet Mars, and beyond. The National Aeronautics and Space Administration (NASA) is developing a set of design reference missions that will provide further detail to these plans. Lunar missions are expected to provide a stepping stone, through operational research and evaluation, in developing the knowledge base necessary to send crews on long duration missions to Mars and other distant destinations. The NASA Exploration Systems Directorate (ExSD), in its program of bioastronautics research, manages the development of technologies that maintain human life, health, and performance in space. Using a systems engineering process and risk management methods, ExSD s Human Support Systems (HSS) Program selects and performs research and technology development in several critical areas and transfers the results of its efforts to NASA exploration mission/systems development programs in the form of developed technologies and new knowledge about the capabilities and constraints of systems required to support human existence beyond Low Earth Orbit. HSS efforts include the areas of advanced environmental monitoring and control, extravehicular activity, food technologies, life support systems, space human factors engineering, and systems integration of all these elements. The HSS Program provides a structured set of deliverable products to meet the needs of exploration programs. these products reduce the gaps that exist in our knowledge of and capabilities for human support for long duration, remote space missions. They also reduce the performance gap between the efficiency of current space systems and the greater efficiency that must be achieved to make human planetary exploration missions economically and logistically feasible. In conducting this research and technology development program, it is necessary for HSS technologists and program managers to develop a common currency for decision making and the allocation of funding. A high level assessment is made of both the knowledge gaps and the system performance gaps across the program s technical project portfolio. This allows decision making that assures proper emphasis areas and provides a key measure of annual technological progress, as exploration mission plans continue to mature.

Berdich, Debra P.↗
NASA NTRS2004

Developing Advanced Human Support Technologies for Planetary Exploration Missions

The United States Vision for Space Exploration calls for sending robots and humans to explore the Earth's moon, the planet Mars, and beyond. The National Aeronautics and Space Administration (NASA) is developing a set of design reference missions that will provide further detail to these plans. Lunar missions are expected to provide a stepping stone, through operational research and evaluation, in developing the knowledge base necessary to send crews on long duration missions to Mars and other distant destinations. The NASA Exploration Systems Directorate (ExSD), in its program of bioastronautics research, manages the development of technologies that maintain human life, health, and performance in space. Using a system engineering process and risk management methods, ExSD's Human Support Systems (HSS) Program selects and performs research and technology development in several critical areas and transfers the results of its efforts to NASA exploration mission/systems development programs in the form of developed technologies and new knowledge about the capabilities and constraints of systems required to support human existence beyond Low Earth Orbit. HSS efforts include the areas of advanced environmental monitoring and control, extravehicular activity, food technologies, life support systems, space human factors engineering, and systems integration of all these elements. The HSS Program provides a structured set of deliverable products to meet the needs of exploration programs. These products reduce the gaps that exist in our knowledge of and capabilities for human support for long duration, remote space missions. They also reduce the performance gap between the efficiency of current space systems and the greater efficiency that must be achieved to make human planetary exploration missions economically and logistically feasible. In conducting this research and technology development program, it is necessary for HSS technologists and program managers to develop a common currency for decision making and the allocation of funding. A high level assessment is made of both the knowledge gaps and the system performance gaps across the program s technical project portfolio. This allows decision making that assures proper emphasis areas and provides a key measure of annual technological progress, as exploration mission plans continue to mature.

Berdich, Debra P.↗
DOE OSTI2019

Decoy exosomes as a novel biologic reagent to antagonize inflammation

Background: Exosomes are ubiquitous naturally secreted stable nanovesicles that can be engineered to target and deliver novel therapeutics to treat a host of human diseases. Methods: We engineered the surfaces of cell-derived nanovesicles to act as decoys in the treatment of inflammation by antagonizing the major proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Results: Decoy exosomes were generated by displaying the TNFα binding domain of human TNF receptor-1 (hTNFR1) on the outer surface of exosomes using stably transfected HEK293 cells. We developed an efficient method to purify the engineered exosomes from conditioned medium based on sequential centrifugation, ultrafiltration, and precipitation. We characterized decoy exosomes using immune-quantification, nanoparticle tracking analysis, and confocal microscopy to confirm that they retain the correct orientation, size, and shape of naturally produced exosomes. We demonstrated the engineered decoy exosomes specifically antagonize activities of TNFα using an inflammatory reporter cell line. Conclusions: Decoy exosomes produced in human cells serve as a novel biologic reagent for antagonizing inflammatory signaling mediated by TNFα.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

Artemis Internal Science Team Update: Deployed Payloads

Artemis will reestablish human presence on the Moon and lead to a new era of scientific discovery and exploration. Led by the National Aeronautics and Space Administration (NASA), the Artemis effort includes a collaboration of space agencies and companies from around the world. In support of Artemis, a cross-disciplinary effort of science, engineering, operations, and human factors personnel is currently developing the best methods, facilities, and field locations to test hardware, train astronauts, and evaluate concepts of operations. This poster, as part of the Artemis Internal Science Team (AIST), provides an update to NASA’s plans for the solicitation, development, and operations of deployed surface payloads. In calendar year 2023, NASA’s Science Mission Directorate will solicit proposals for instruments to be deployed by crew on the surface of the Moon (Fig. 1), beginning with Artemis III. The Artemis III mission will land in the south polar region of the Moon, within 6º of latitude from the south pole, in the vicinity of both persistently illuminated and permanently shadowed areas of the Moon, with potential access to surface-accessible volatile deposits. Several of the proposed landing regions are located among some of the oldest parts of the Moon, and together with the permanently shadowed regions, provide the opportunity to learn about the history of the Moon through previously unexplored lunar regions. Deployed payloads will be a critical part of a notional program that captures the highest-priority science for Artemis III and provides the greatest feed-forward to follow-on missions and the build-up to the Artemis Base Camp.

R. C. Weber↗
NASA NTRSDate not supplied

Artemis Internal Science Team Update: Hardware and Integrated Testing

The Artemis program will reestablish human presence on the Moon and lead to a new era of scientific discovery and exploration. Led by the National Aeronautics and Space Administration (NASA), the Artemis program is a collaboration of space agencies and companies from around the world. In support of the Artemis program a cross disciplinary effort integrating science, engineering, operations, and human factors is currently being developed to identify methods, facilities, and field locations to test hardware, train astronauts, and evaluate concepts of operations. NASA’s Science Mission Directorate (SMD) and Exploration Systems Development Mission Directorate (ESDMD) established a comprehensive Science Team structure to support the Artemis program. This structure includes 1) an Artemis Internal Science Team (AIST), 2) a Geology Team (GT) with additional Participating Scientists (PS) roles, and 3) Payload Teams (PT) for the inclusion of scientific instruments. The GT, PS and PT will be competitively selected for each mission as part of NASA’s Research Opportunities in Space and Earth Sciences (ROSES) solicitations. The AIST provides multi-mission continuity and has been working closely with Artemis program elements to best integrate science into all aspects of planning and development. This abstract serves to provide an AIST update on science relevant hardware developments and integrated testing efforts that occurred in 2022.

Trevor George Graff↗
NASA NTRSDate not supplied

Artemis Internal Science Team Update: Deployed Payloads

Artemis will reestablish human presence on the Moon and lead to a new era of scientific discovery and exploration. Led by the National Aeronautics and Space Administration (NASA), the Artemis effort includes a collaboration of space agencies and companies from around the world [1]. In support of Artemis, a cross-disciplinary effort of science, engineering, operations, and human factors personnel is currently developing the best methods, facilities, and field locations to test hardware, train astronauts, and evaluate concepts of operations. This abstract, as part of the Artemis Internal Science Team (AIST) [2], provides an update to NASA’s plans for the solicitation, development, and operations of deployed surface payloads. In calendar year 2023, NASA’s Science Mission Directorate will solicit proposals for instruments to be deployed by crew on the surface of the Moon (Fig. 1), beginning with Artemis III [3]. The Artemis III mission will land in the south polar region of the Moon, within 6º of latitude from the south pole, in the vicinity of both persistently illuminated and permanently shadowed areas of the Moon, with potential access to surface-accessible volatile deposits [4]. Several of the proposed landing regions are located among some of the oldest parts of the Moon, and together with the permanently shadowed regions, provide the opportunity to learn about the history of the Moon through previously unexplored lunar regions [5]. Deployed payloads will be a critical part of a notional program that captures the highest-priority science for Artemis III and provides the greatest feedforward to follow-on missions and the build-up to the Artemis Base Camp

R. C. Weber↗
DOE OSTI2017

Ensuring operator reliability in digital control rooms - 102

The U.S. fleet of nuclear power plants is aging, and efforts are being made to modernize instrumentation and control systems including integration of digital human-machine interfaces (HMIs) into the control room. Automation and control technologies have advanced since original systems were installed in the plants. This presents unique opportunities and challenges in ensuring the replacements are a benefit to the operators and the overall safe and reliable operation of the plant. We discuss trends we have observed from assisting utilities in their modernization efforts. Automation and evolving control rooms come with their own host of problems that existing human factors and engineering methods fail to capture. Traditional approaches are analytical approaches to ensuring reliability. Here we discuss some of the shortfalls of these traditional approaches as plants become increasingly more complex. We suggest that ensuring reliability for modernized and next generation control room will require expanding the scope of what was traditionally considered human factors as well as exploring novel approaches and methodologies for dealing with complexity and rapidly advancing technology. (authors)

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
NASA NTRS2010

Rocket + Science = Dialogue

It's a cliche that rocket engineers and space scientists don t see eye-to-eye. That goes double for rocket engineers working on human spaceflight and scientists working on space telescopes and planetary probes. They work fundamentally different problems but often feel that they are competing for the same pot of money. Put the two groups together for a weekend, and the results could be unscientific or perhaps combustible. Fortunately, that wasn't the case when NASA put heavy lift launch vehicle designers together with astronomers and planetary scientists for two weekend workshops in 2008. The goal was to bring the top people from both groups together to see how the mass and volume capabilities of NASA's Ares V heavy lift launch vehicle could benefit the science community. Ares V is part of NASA's Constellation Program for resuming human exploration beyond low Earth orbit, starting with missions to the Moon. In the current mission scenario, Ares V launches a lunar lander into Earth orbit. A smaller Ares I rocket launches the Orion crew vehicle with up to four astronauts. Orion docks with the lander, attached to the Ares V Earth departure stage. The stage fires its engine to send the mated spacecraft to the Moon. Standing 360 feet high and weighing 7.4 million pounds, NASA's new heavy lifter will be bigger than the 1960s-era Saturn V. It can launch almost 60 percent more payload to translunar insertion together with the Ares I and 35 percent more mass to low Earth orbit than the Saturn V. This super-sized capability is, in short, designed to send more people to more places to do more things than the six Apollo missions.

Morris,Bruce↗
DOE OSTI2021

Human-Constrained Indicators of Gatekeeping Behavior as a Role in Information Suppression: Finding Invisible Information and the Significant Unsaid

To date, disinformation research has focused largely on the production of false information ignoring the suppression of select information. We term this alternative form of disinformation information suppression. Information suppression occurs when facts are withheld with the intent to mislead. In order to detect information suppression, we focus on understanding the actors who withhold information. In this research, we use knowledge of human behavior to find signatures of different gatekeeping behaviors found in text. Specifically, we build a model to classify the different types of edits on Wikipedia using the added text alone and compare a human-informed feature engineering approach to a featureless algorithm. Being able to computationally distinguish gatekeeping behaviors is a first step towards identifying when information suppression is occurring.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗