Search NASA⌕ Search

SEARCH · Search NASA

Results for “shared control”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Technical Specification Surveillance Interval Extension Using Self-Diagnostics

As part of the Light Water Reactor Sustainability program, an ongoing research effort is being conducted on technical specifications surveillance interval extension of digital equipment in nuclear power plants. The research team is led by Idaho National Laboratory and includes Pacific Northwest National Laboratory, Technology Resources, and Oak Ridge National Laboratory. This research focuses on developing methods for applying the U.S. Nuclear Regulatory Commission (NRC)–approved guidance to implement a licensee-controlled, risk-informed surveillance frequency change program in digital instrumentation and control (I&C) systems that include self-diagnostics and online monitoring (OLM) capabilities. Although approved methods exist for extending technical specifications (TS) surveillance test intervals (STIs) for general equipment, including analog I&C equipment, gaps remain in technology and guidance on crediting newer digital equipment’s internal self-diagnostics and OLM characteristics. Previous research described a general methodology for crediting internal self-diagnostics for extending surveillance test intervals. The methodology used self-diagnostics to detect—and credited recovery from—failure. Self-diagnostics were also applied for performance monitoring during the extended surveillance interval. This report discusses the status of recent activities to evaluate the previously developed methodology using a pilot study. Although both a utility partner for a pilot study and a specific digital asset were identified in FY2020, delays in obtaining proprietary information resulted in a limited ability to fully evaluate the methodology, and further interactions were complicated by the COVID pandemic. Therefore, at that time, the use of public-domain information—along with current processes for surveillance interval extension through a surveillance frequency control program—identified the need to fully assess diagnostic coverage as part of the pilot study. Furthermore, self-diagnostics were also identified as a potential option to replace the drift analyses conducted as part of current STI extension procedures. In FY2022, the project was reconstituted with the industry partner, and information and data were made available by the industry partner to the research team for review. The shared information included failure event descriptions and data for a digital I&C system since its implementation, as well as recent STI extension interval reports developed by the utility partner on that digital I&C system. This report presents an evaluation of this information and data and describes an application of the proposed methodology cited above. The methodology seeks to take advantage of the self-diagnostics and OLM capabilities to reduce risk or reduce the level of qualitative monitoring assessment needed to perform a risk-informed STI extension using existing NRC approved guidance or both. Addressing these issues of STI extension by crediting self-diagnostics is likely to result in benefits for current and future nuclear power plant (NPP) operations, including lowering the barriers to adoption of digital I&C systems and increasing cost savings by deferring or eliminating unneeded preventive maintenance (tasks or checks or activities). Specifically, self-diagnostic and OLM capabilities of newer digital equipment being installed in non-safety and safety applications are designed to detect failures, provide early warning of potential failures, and notify plant operators to take appropriate action to reduce out of service (OOS) time thus protecting safety margins. Moreover, the equipment is expected to provide information that time-related operational degradation is identified early to ensure timely and planned corrective actions instead of a reactive and unplanned approach ahead of an extended-surveillance interval.

42 ENGINEERING↗
DOE OSTI2026

Shaping the FutureWorkforce: Challenges and Lessons Learned in HPC Education from National Labs and Computing Centers

Workforce training at national laboratories and computing centers is essential and typically falls into two categories: foundational training for newcomers and advanced training for experienced users. Foundational topics—such as version control, build systems, and basic HPC usage—are largely transferable across institutions, while cluster-specific training varies due to differences in hardware, job schedulers, and local workflows. Training on emerging technologies is split between hardware-specific content and broadly applicable programming paradigms. Here, to reduce redundancy and increase impact, national labs, computing centers, and vendors are collaborating through initiatives like the HPC Training Working Group to share best practices, co-develop materials, and broaden outreach. These coordinated efforts aim to make HPC training more accessible, scalable, and consistent across the community.

HPC↗
NASA NTRS1989

A robot arm simulation with a shared memory multiprocessor machine

A parallel processing scheme for a single chain robot arm is presented for high speed computation on a shared memory multiprocessor. A recursive formulation that is derived from a virtual work form of the d'Alembert equations of motion is utilized for robot arm dynamics. A joint drive system that consists of a motor rotor and gears is included in the arm dynamics model, in order to take into account gyroscopic effects due to the spinning of the rotor. The fine grain parallelism of mechanical and control subsystem models is exploited, based on independent computation associated with bodies, joint drive systems, and controllers. Efficiency and effectiveness of the parallel scheme are demonstrated through simulations of a telerobotic manipulator arm. Two different mechanical subsystem models, i.e., with and without gyroscopic effects, are compared, to show the trade-off between efficiency and accuracy.

Kim, Sung-Soo↗
NASA NTRS1996

User-Centered Indexing for Adaptive Information Access

We are focusing on information access tasks characterized by large volume of hypermedia connected technical documents, a need for rapid and effective access to familiar information, and long-term interaction with evolving information. The problem for technical users is to build and maintain a personalized task-oriented model of the information to quickly access relevant information. We propose a solution which provides user-centered adaptive information retrieval and navigation. This solution supports users in customizing information access over time. It is complementary to information discovery methods which provide access to new information, since it lets users customize future access to previously found information. It relies on a technique, called Adaptive Relevance Network, which creates and maintains a complex indexing structure to represent personal user's information access maps organized by concepts. This technique is integrated within the Adaptive HyperMan system, which helps NASA Space Shuttle flight controllers organize and access large amount of information. It allows users to select and mark any part of a document as interesting, and to index that part with user-defined concepts. Users can then do subsequent retrieval of marked portions of documents. This functionality allows users to define and access personal collections of information, which are dynamically computed. The system also supports collaborative review by letting users share group access maps. The adaptive relevance network provides long-term adaptation based both on usage and on explicit user input. The indexing structure is dynamic and evolves over time. Leading and generalization support flexible retrieval of information under similar concepts. The network is geared towards more recent information access, and automatically manages its size in order to maintain rapid access when scaling up to large hypermedia space. We present results of simulated learning experiments.

Chen, James R.↗
NASA NTRS2004

Four-Channel PC/104 MIL-STD-1553 Circuit Board

The mini bus interface card (miniBIC) is the first four-channel electronic circuit board that conforms to MIL-STD-1553 and to the electrical-footprint portion of PC/104. [MIL-STD-1553 is a military standard that encompasses a method of communication and electrical- interface requirements for digital electronic subsystems connected to a data bus. PC/104 is an industry standard for compact, stackable modules that are fully compatible (in architecture, hardware, and software) with personal-computer data- and power-bus circuitry.] Prior to the development of the miniBIC, only one- and two-channel PC/104 MIL-STD-1553 boards were available. To obtain four channels, it was necessary to include at least two boards in a PC/104 stack. In comparison with such a two-board stack, the miniBIC takes up less space, consumes less power, and is more reliable. In addition, the miniBIC includes 32 digital input/output channels. The miniBIC (see figure) contains four MIL-STD-1553B hybrid integrated circuits (ICs), four transformers, a field-programmable gate array (FPGA), and an Industry Standard Architecture (ISA) interface. Each hybrid IC includes a MILSTD-1553 dual transceiver, memory-management circuitry, processor interface logic circuitry, and 64Kx16 bits of shared static random access memory. The memory is used to configure message and data blocks. In addition, 23 16-bit registers are available for (1) configuring the hybrid IC for, and starting it in, various modes of operation; (2) reading the status of the functionality of the hybrid IC; and (3) resetting the hybrid IC to a known state. The miniBIC can operate as a remote terminal, bus controller, or bus monitor. The FPGA provides the chip-select and data-strobe signals needed for operation of the hybrid ICs. The FPGA also receives interruption signals and forwards them to the ISA bus. The ISA interface connects the address, data, and control interfaces of the hybrid ICs to the ISA backplane. Each channel is, in effect, a MIL-STD-1553 interface that can operate either independently of the others or else as a redundant version of one of the others. The transformer in each channel provides electrical isolation between the rest of the miniBIC circuitry and the bus to which that channel is connected.

Cox, Gary L.↗
DOE OSTI2020

Phosphoproteome Response to Dithiothreitol Reveals Unique Versus Shared Features of Saccharomyces cerevisiae Stress Responses

To cope with sudden changes in the external environment, the budding yeast Saccharomyces cerevisiae orchestrates a multifaceted response that spans many levels of physiology. Several studies have interrogated the transcriptome response to endoplasmic reticulum (ER) stress and the role of regulators such as the Ire1 kinase and Hac1 transcription factors. However, less is known about responses to ER stress at other levels of physiology. Here, we used quantitative phosphoproteomics and computational network inference to uncover the yeast phosphoproteome response to the reducing agent dithiothreitol (DTT) and the upstream signaling network that controls it. We profiled wild-type cells and mutants lacking IRE1 or MAPK kinases MKK1 and MKK2, before and at various times after DTT treatment. In addition to revealing downstream targets of these kinases, our inference approach predicted new regulators in the DTT response, including cell-cycle regulator Cdc28 and osmotic-response kinase Rck2, which we validated computationally. Our results also revealed similarities and surprising differences in responses to different stress conditions, especially in the response of protein kinase A targets. Furthermore, these results have implications for the breadth of signaling programs that can give rise to common stress response signatures.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

Spacecraft Line-Of-Sight Jitter Mitigation and Management Lessons Learned and Engineering Best Practices

Predicting, managing, controlling, and testing spacecraft line-of-sight (LoS) jitter caused by micro-vibrations due to onboard internal disturbance sources is a formidable multidisciplinary engineering task. It is especially challenging for those missions hosting high-performance, vibration-sensitive optical sensor payloads with stringent pointing stability requirements. Both NASA and ESA are planning technically aggressive spaceflight missions that include ultra-high-performance optical payloads with delicate, highly vibration-sensitive scientific and observational instruments. The GN&C community of practice will need to leverage and build upon their collective experiences and lessons learned to better address future micro-vibration challenges. To identify lessons learned and best engineering practices the NASA Engineering & Safety Center (NESC) sponsored a two-day Spacecraft LoS Jitter Workshop in late 2019. The workshop’s goal was to provide a multidisciplinary forum to elicit deeper understanding of the issues related to solving the spacecraft LoS jitter/micro-vibration problem. A primary objective was to identify and share best practices, rules of thumb, and options for jitter-related activities. Representatives from NASA, JPL, ESA, along with NASA’s industrial partners, independent consultant subject matter experts, and members of academia participated in the workshop. This paper will describe the motivation for the NASA Spacecraft LoS Jitter Workshop and summarize the identified findings, observations, and recommendations.

Lessons Learned;↗
DOE OSTI2021

Submerging islands through thermalization

We illustrate scenarios in which Hawking radiation collected in finite regions of a reservoir provides temporary access to the interior of black holes through transient entanglement “islands.” Whether these islands appear and the amount of time for which they dominate — sometimes giving way to a thermalization transition — is controlled by the amount of radiation we probe. In the first scenario, two reservoirs are coupled to an eternal black hole. The second scenario involves two holographic quantum gravitating systems at different temperatures interacting through a Rindler-like reservoir, which acts as a heat engine maintaining thermal equilibrium. The latter situation, which has an intricate phase structure, describes two eternal black holes radiating into each other through a shared reservoir.

2D gravity↗
DOE OSTI2011

Quantum tagging for tags containing secret classical data

Various authors have considered schemes for quantum tagging, that is, authenticating the classical location of a classical tagging device by sending and receiving quantum signals from suitably located distant sites, in an environment controlled by an adversary whose quantum information processing and transmitting power is potentially unbounded. All of the schemes proposed elsewhere in the literature assume that the adversary is able to inspect the interior of the tagging device. All of these schemes have been shown to be breakable if the adversary has unbounded predistributed entanglement. We consider here the case in which the tagging device contains a finite key string shared with distant sites but kept secret from the adversary, and show this allows the location of the tagging device to be authenticated securely and indefinitely. Our protocol relies on quantum key distribution between the tagging device and at least one distant site, and demonstrates a new practical application of quantum key distribution. It also illustrates that the attainable security in position-based cryptography can depend crucially on apparently subtle details in the security scenario considered.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2017

Water Quality Projects Summary for the Mid-Columbia and Cumberland River Systems

Scheduling and operational control of hydropower systems is accompanied with a keen awareness of the management of water use, environmental effects, and policy, especially within the context of strict water rights policy and generation maximization. This is a multi-objective problem for many hydropower systems, including the Cumberland and Mid-Columbia river systems. Though each of these two systems have distinct operational philosophies, hydrologic characteristics, and system dynamics, they both share a responsibility to effectively manage hydropower and the environment, which requires state-of-the art improvements in the approaches and applications for water quality modeling. The Department of Energy and Oak Ridge National Laboratory have developed tools for total dissolved gas (TDG) prediction on the Mid-Columbia River and a decision-support system used for hydropower generation and environmental optimization on the Cumberland River. In conjunction with IIHR - Hydroscience & Engineering, The University of Iowa and University of Colorado s Center for Advanced Decision Support for Water and Environmental Systems (CADSWES), ORNL has managed the development of a TDG predictive methodology at seven dams along the Mid-Columbia River and has enabled the ability to utilize this methodology for optimization of operations at these projects with the commercially available software package Riverware. ORNL has also managed the collaboration with Vanderbilt University and Lipscomb University to develop a state-of-the art method for reducing high-fidelity water quality modeling results into surrogate models which can be used effectively within the context of optimization efforts to maximize generation for a reservoir system based on environmental and policy constraints. The novel contribution of these efforts is the ability to predict water quality conditions with simplified methodologies at the same level of accuracy as more complex and resource intensive computing methods. These efforts were designed to incorporate well into existing hydropower and reservoir system scheduling models, with runtimes that are comparable to existing software tools. In addition, the transferability of these tools to assess other systems is enhanced due the use of simplistic and easily attainable values for inputs, straight-forward calibration of predictive equation coefficients, and standardized comparison of traditionally familiar outputs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Pentalum SpiDAR Deployment at the SWiFT Facility FY19

The Texas Tech University (TTU) research group is actively studying wind turbine wake development, as part of developing innovative wake control strategies to improve the performance of wind farms. The team has a set of eight ground lidars to perform field measurements at the Sandia National Laboratories SWiFT site. This document describes tests details including configurations, timeframe, hardware, and the required collaboration from the Sandia team. This test plan will facilitate the coordination between both TTU and the Sandia team in terms of site accessibility, staff training, and data sharing to meet the specific objectives of the tests.

Pol, Suhas↗
DOE OSTI2019

Shell Element Material Model Verification Problems for DYNA3D

A suite of shell element material model verification tests were developed for the explicit finite element program DYNA3D. Each test consists of a single quadrilateral shell element, whose nodal displacements and rotations have been prescribed such that the deformation of the material is fully controlled throughout the analysis. At one of the element’s integration points, the numerically computed stress, through-thickness strain, and equivalent plastic strain are compared against closed-form reference solutions that are derived to be consistent with the theory of finite deformation elasto-plasticity. A collection of 31 feature-specific verification tests are proposed, each of which may be used to verify all models which share in common the tested feature of interest. For each material model, a subset of these tests are selected and used to verify the correct behavior of all features of the model. The collective suite of tests cover 26 of the 27 currently available material models in DYNA3D. In the course of developing the proposed test suite, 18 implementation bugs were identified and have subsequently been resolved.

42 ENGINEERING↗
DOE OSTI2020

Status Report on IES Plug-and-Play Framework

This report discusses the status of the flexible plug-and-play framework development currently ongoing that aims to integrate Modelica/Dymola with the Risk Analysis and Virtual ENviroment (RAVEN) software in terms of both Functional Mock-Up Interface (FMI)/Functional Mock-Up Unit (FMU) construction and repository structures that aim to ease the sharing and simulation of complex dynamic models. This report provides discusses the FMI/FMU adaptors that have been created within the HYBRID repository to allow users to quickly export models as FMUs. Several examples are shown that highlight the step-by-step process of converting an existing Modelica model into an FMU for use within the Dymola platform. Simulation results demonstrate that, while minor differences may occur, the overall control, trends, and solution integrity is maintained between standard Modelica simulation and FMU simulation results. However, it is worth noting that, for small systems, the FMU results have a slower simulation time than the Modelica only simulation. Using this process, a company can provide models that contain proprietary information to entities without disclosing any of the information about the model that could be considered business sensitive. Such an ability would allow institutions to bypass the necessity of “whitewashing” data. In addition to the investigative work being conducted on FMUs and FMIs, a series of updates to the hybrid repository has been completed. These updates include the addition of Modelica system-level regression tests and software quality assurance documentation that ensure that modifications to the Modelica models do not alter system-level model results. Overall, extensive work has been completed on developing FMUs and FMIs from existing models, understanding the requirements and limitations of FMUs, and opensourcing the HYBRID repository with an integrated regression system.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2019

A Salt Repository Concept for CSNF in 21-PWR Size Canisters

The most straightforward concept for disposal of large, heavy packages containing commercial spent nuclear fuel (CSNF) in a repository in bedded salt, would be to emplace them directly on the floor in emplacement tunnels. In-tunnel axially aligned horizontal emplacement would minimize excavated volume and avoid drilling of large-diameter emplacement boreholes. A similar concept was proposed in Germany for direct disposal of POLLUX ® canisters. The repository would be constructed at a depth of 500 to 1,000 m for isolation from the surface, and for sufficient overburden stress to ensure creep reconsolidation of repository openings. It could entail modular panels of emplacement tunnels arranged on headings oriented in cardinal directions from a central core, to accommodate the estimated 140,000 MTU total U.S. CSNF inventory. To do so, the overall area of the repository layout would be approximately 20 km 2 . Many layouts are possible, but the approach should be modular, excavation should be deferred for as long as possible to avoid maintenance, and the emplacement areas should share support facilities and shafts. Vertical shafts would be used in accordance with mining practice in sedimentary basins. Large diameter shafts would be needed for ventilation exhaust and waste transport, with smaller shafts for waste salt removal, men & materials, and ventilation intake. The spacing between disposal tunnels as estimated from thermal modeling, seeks to limit the maximum average areal thermal load in the panels to 11 W/m 2 to control long-term heat buildup in the host rock. Peak salt temperature would occur within a few years and would be dominated by each waste package locally, simplifying thermal management. There would be some flexibility to decrease the package spacing or increase the emplacement thermal power limit Backfilling emplaced waste packages immediately with mine-run crushed salt would provide shielding and expedite reconsolidation. This arrangement would isolate adjacent waste packages from one another by the intervening backfill, especially after it reconsolidates and its properties approach those of intact salt. After the repository is fully loaded and the performance confirmation program is complete, activities to permanently close the repository would be initiated. During closure operations all openings in the host salt would be backfilled, then shafts would be sealed, and boreholes plugged. Plans for the Waste Isolation Pilot Plant (WIPP) show how sealing and plugging could be done. A monitoring program could continue for 50 years or longer after repository closure. With an emplacement thermal power limit of 10 kW per waste package, nearly all the CSNF that is projected to be produced by the current fleet of reactors in the U.S. could be emplaced over a period of approximately 50 years starting in calendar 2048. No barriers to implementation in a reasonable timeframe have been identified from this generic analysis. Engineering challenges include: 1) shaft construction; 2) a very-large capacity shaft hoist; 3) overpack design; 4) a transport-emplacement-vehicle (TEV) for transporting waste packages once they are underground and emplacing them remotely; and 5) remotely operated equipment for emplacing backfill. The method of shaft construction would depend on site-specific conditions, and could involve freezing the subsurface. A shaft hoist with payload capacity of 175 MT seems technically and economically feasible based on development work in Germany, and it would be the largest hoist of its kind. The function of disposal overpacks would be to provide reliable containment during repository operations, which could be accomplished using a corrosion allowance material such as a low-carbon steel. Development effort would be needed to determine overpack thickness (e.g., 7 to 20 cm) that can resist corrosion and loading from salt creep, to rovide containment throughout the repository operational period. The transport-emplacement vehicle (TEV) would be similar to previous concepts, particularly one option proposed for a Yucca Mountain repository. It would move over a rough salt floor on independently driven and steered wheels, and carry heavy shielding in addition to a waste package. By analogy to the safety case for the WIPP in New Mexico, human intrusion is likely to be the dominant mode of radionuclide release from the repository. Treatment of human intrusion for a CSNF repository in salt could depend on promulgation of site-specific changes in the regulations. Radionuclide release and migration would be quite limited for undisturbed conditions. There may be opportunities for improved understanding of salt performance with waste heating, based on future in situ testing in an underground salt research laboratory. This report also discusses a developing area of salt rock mechanics that involves low-stress, low strain-rate creep that might cause large, heavy waste packages to slowly sink. Site-specific sampling, testing, and modeling would be used to determine if the mechanism is important enough to merit consideration in design, or inclusion in performance assessment. Part of engineering design and postclosure safety assessment for a CSNF repository in salt would be to implement a methodology to show that the probability of a criticality event in the repository, when waste packages eventually breach and are flooded, is less than the probability screening threshold for performance assessment. In the methodology, a criticality analysis would be performed for waste packages in the repository, incorporating measures that could be introduced as needed to limit reactivity, for example using fuel selection and loading rules, and crediting the absorption of thermal neutrons by natural chlorine in the environment. A similar analysis has been underway for CSNF stored in dual-purpose canisters. Ideally the strategy would be developed prior to actually loading SNF assemblies into canisters used in waste packages for disposal.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
NASA NTRS2009

A Theoretical Investigation of Composite Overwrapped Pressure Vessel (COPV) Mechanics Applied to NASA Full Scale Tests

A theoretical investigation of the factors controlling the stress rupture life of the National Aeronautics and Space Administration's (NASA) composite overwrapped pressure vessels (COPVs) continues. Kevlar (DuPont) fiber overwrapped tanks are of particular concern due to their long usage and the poorly understood stress rupture process in Kevlar filaments. Existing long term data show that the rupture process is a function of stress, temperature and time. However due to the presence of a load sharing liner, the manufacturing induced residual stresses and the complex mechanical response, the state of actual fiber stress in flight hardware and test articles is not clearly known. This paper is a companion to a previously reported experimental investigation and develops a theoretical framework necessary to design full-scale pathfinder experiments and accurately interpret the experimentally observed deformation and failure mechanisms leading up to static burst in COPVs. The fundamental mechanical response of COPVs is described using linear elasticity and thin shell theory and discussed in comparison to existing experimental observations. These comparisons reveal discrepancies between physical data and the current analytical results and suggest that the vessel s residual stress state and the spatial stress distribution as a function of pressure may be completely different from predictions based upon existing linear elastic analyses. The 3D elasticity of transversely isotropic spherical shells demonstrates that an overly compliant transverse stiffness relative to membrane stiffness can account for some of this by shifting a thin shell problem well into the realm of thick shell response. The use of calibration procedures are demonstrated as calibrated thin shell model results and finite element results are shown to be in good agreement with the experimental results. The successes reported here have lead to continuing work with full scale testing of larger NASA COPV hardware.

Thesken, John C.↗
NASA NTRS2010

Tissuelike 3D Assemblies of Human Broncho-Epithelial Cells

Three-dimensional (3D) tissuelike assemblies (TLAs) of human broncho-epithelial (HBE) cells have been developed for use in in vitro research on infection of humans by respiratory viruses. The 2D monolayer HBE cell cultures heretofore used in such research lack the complex cell structures and interactions characteristic of in vivo tissues and, consequently, do not adequately emulate the infection dynamics of in-vivo microbial adhesion and invasion. In contrast, the 3D HBE TLAs are characterized by more-realistic reproductions of the geometrical and functional complexity, differentiation of cells, cell-to-cell interactions, and cell-to-matrix interactions characteristic of human respiratory epithelia. Hence, the 3D HBE TLAs are expected to make it possible to perform at least some of the research in vitro under more-realistic conditions, without need to infect human subjects. The TLAs are grown on collagen-coated cyclodextran microbeads under controlled conditions in a nutrient liquid in the simulated microgravitational environment of a bioreactor of the rotating- wall-vessel type. Primary human mesenchymal bronchial-tracheal cells are used as a foundation matrix, while adult human bronchial epithelial immortalized cells are used as the overlying component. The beads become coated with cells, and cells on adjacent beads coalesce into 3D masses. The resulting TLAs have been found to share significant characteristics with in vivo human respiratory epithelia including polarization, tight junctions, desmosomes, and microvilli. The differentiation of the cells in these TLAs into tissues functionally similar to in vivo tissues is confirmed by the presence of compounds, including villin, keratins, and specific lung epithelium marker compounds, and by the production of tissue mucin. In a series of initial infection tests, TLA cultures were inoculated with human respiratory syncytial viruses and parainfluenza type 3 viruses. Infection was confirmed by photomicrographs that showed signs of damage by viruses and virus titers (see figure) that indicated large increases in the populations of viruses during the days following inoculation.

Goodwin, Thomas J.↗
DOE OSTI2016

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila

Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'–5']pA[3'–5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells. Animal genomes typically encode multiple proteins with predicted homology to cGAS, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'–5']pA[2'–5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.

59 BASIC BIOLOGICAL SCIENCES↗