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At least 19 records

High Level Architecture (HLA) as a Research Tool for Advanced Air Mobility (AAM)

In this document, a NASA investigation into the High-Level Architecture (HLA) standard for distributed simulation as a means of furthering Advanced Air Mobility (AAM) research is illustrated along with a description of the evolution of distributed simulation leading to the HLA standard. HLA enables efficient definition and insertion of components and participants in simulation sessions. Novel concepts can be added or removed as the work evolves. A general history of the HLA standard is described to show past needs for improved methods of distributed simulation, particularly among participating laboratories in separate locations, as well as previous applications of HLA simulation to airspace research. These examples from the past illustrate how new and emerging concepts can be simulated by layering notional ideas over simulated current-day systems and capabilities in a controlled environment for examination. In the 1990s, the Federal Aviation Administration (FAA) and the MITRE Corporation performed joint research into then-emergent capabilities in the National Airspace System (NAS). In the early 2000s, the MITRE Corporation developed an open, extendable set of objects and protocols designed for global and collaborative aviation research called AviationSimNet, which has HLA as its foundation. This led to NASA and the FAA using AviationSimNet to connect laboratories for AAM research, resulting in the NASA/FAA Laboratory Integrated Test Environment (NFLITE). The underlying capabilities of HLA enabled testing a notional interaction between AAM and legacy ATC systems that resulted in AAM vehicles receiving beacon codes for identification on ATC screens in Class C airspace. The potential next steps in this work include defining and examining notional interactions between AAM and legacy ATC systems within Class B airspace.

UAM

An Evaluation of the High Level Architecture (HLA) as a Framework for NASA Modeling and Simulation

The High Level Architecture (HLA) is a current US Department of Defense and an industry (IEEE-1516) standard architecture for modeling and simulations. It provides a framework and set of functional rules and common interfaces for integrating separate and disparate simulators into a larger simulation. The goal of the HLA is to reduce software costs by facilitating the reuse of simulation components and by providing a runtime infrastructure to manage the simulations. In order to evaluate the applicability of the HLA as a technology for NASA space mission simulations, a Simulations Group at Goddard Space Flight Center (GSFC) conducted a study of the HLA and developed a simple prototype HLA-compliant space mission simulator. This paper summarizes the prototyping effort and discusses the potential usefulness of the HLA in the design and planning of future NASA space missions with a focus on risk mitigation and cost reduction.

Reid, Michael R.

Promoting A-Priori Interoperability of HLA-Based Simulations in the Space Domain: The SISO Space Reference FOM Initiative

Distributed and Real-Time Simulation plays a key-role in the Space domain being exploited for missions and systems analysis and engineering as well as for crew training and operational support. One of the most popular standards is the 1516-2010 IEEE Standard for Modeling and Simulation (M&S) High Level Architecture (HLA). HLA supports the implementation of distributed simulations (called Federations) in which a set of simulation entities (called Federates) can interact using a Run-Time Infrastructure (RTI). In a given Federation, a Federate can publish and/or subscribes objects and interactions on the RTI only in accordance with their structures as defined in a FOM (Federation Object Model). Currently, the Space domain is characterized by a set of incompatible FOMs that, although meet the specific needs of different organizations and projects, increases the long-term cost for interoperability. In this context, the availability of a reference FOM for the Space domain will enable the development of interoperable HLA-based simulators for related joint projects and collaborations among worldwide organizations involved in the Space domain (e.g. NASA, ESA, Roscosmos, and JAXA). The paper presents a first set of results achieved by a SISO standardization effort that aims at providing a Space Reference FOM for international collaboration on Space systems simulations.

Moller, Bjorn

On the Execution Control of HLA Federations using the SISO Space Reference FOM

In the Space domain the High Level Architecture (HLA) is one of the reference standard for Distributed Simulation. However, for the different organizations involved in the Space domain (e.g. NASA, ESA, Roscosmos, and JAXA) and their industrial partners, it is difficult to implement HLA simulators (called Federates) able to interact and interoperate in the context of a distributed HLA simulation (called Federation). The lack of a common FOM (Federation Object Model) for the Space domain is one of the main reasons that precludes a-priori interoperability between heterogeneous federates. To fill this lack a Product Development Group (PDG) has been recently activated in the Simulation Interoperability Standards Organization (SISO) with the aim to provide a Space Reference FOM (SRFOM) for international collaboration on Space systems simulations. Members of the PDG come from several countries and contribute experiences from projects within NASA, ESA and other organizations. Participants represent government, academia and industry. The paper presents an overview of the ongoing Space Reference FOM standardization initiative by focusing on the solution provided for managing the execution of an SRFOM-based Federation.

Moller, Bjorn

wavess 1.2: presenting an HLA-aware within-host virus sequence simulation framework

Motivation Understanding how virus sequences are shaped by selection can inform vaccine design and transmission inference. Modeling within-host evolution to interrogate these questions requires a detailed mechanistic framework that accurately captures sequence diversification. The CD8 + cytotoxic T-lymphocyte (CTL) response plays an important role in immune-mediated selection and can leave strong signatures in virus sequences; however, existing sequence-based within-host virus modeling frameworks do not explicitly include a human leukocyte antigen (HLA)-aware CTL response. Results We extended our previously published within-host sequence evolution simulator, wavess, to include an explicit CTL response, and share a method for identifying HLA-specific CTL epitopes given a founder virus sequence. We also updated the model to permit a variable recombination rate, which allows for modeling non-adjacent genes, segmented genomes, and recombination hotspots. These extensions to wavess allow for more accurate simulation of viruses and virus genes, particularly in regions of the genome where the immune response is dominated by CTLs (rather than antibodies). It also provides the foundation for investigations of how these newly-added biological mechanisms influence within-host evolution. Availability and implementation The core of wavess is written in Python 3, with helper functions written in R. It is available at https://github.com/MolEvolEpid/wavess.

60 APPLIED LIFE SCIENCES

Quantification of heterogeneity in human CD8 + T cell responses to vaccine antigens: an HLA-guided perspective

Vaccines have historically played a pivotal role in controlling epidemics. Effective vaccines for viruses causing significant human disease, e.g., Ebola, Lassa fever, or Crimean Congo hemorrhagic fever virus, would be invaluable to public health strategies and counter-measure development missions. Here, we propose coverage metrics to quantify vaccine-induced CD8 + T cell-mediated immune protection, as well as metrics to characterize immuno-dominant epitopes, in light of human genetic heterogeneity and viral evolution. Proof-of-principle of our approach and methods are demonstrated for Ebola virus, SARS-CoV-2, and Burkholderia pseudomallei (vaccine) proteins.

60 APPLIED LIFE SCIENCES

Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance

Introduction Clinical use of several small molecule drugs may lead to severe T-cell-mediated idiosyncratic drug hypersensitivity reactions (iDHR) linked to HLA alleles, including abacavir (ABC) with HLA-B*57:01. Due to study limitations in humans, pathogenic networks in iDHR remain elusive. HLA transgenic murine models have been proposed to bridge knowledge gaps in tolerance and susceptibility to drugs. Methods Mice expressing HLA-B*57:01 and Foxp3-DTR/EGFP were generated to selectively deplete regulatory T-cells (Treg) with diphtheria toxin. ABC was administered for 8 days alone or together with cell- and cytokine-depleting antibodies. Cellular and transcriptomic responses were analyzed by RNA, flow cytometry and fluorescence methods. Results While CD8 + T-cell responses to ABC require HLA presentation, ABC also triggered mitochondrial stress in macrophagesin vitro, independently of HLA.In vivo, Treg were the primary mechanism of drug tolerance controlling HLA presentation and costimulation by antigen presenting cells. Treg ablation uncovered immune adverse events linked to activation and proliferation of both drug-specific and bystander CD8 + T-cells through CD28-mediated pathways with support from CD4 + non-Treg. Type-I interferon (IFN-I) and cellular-stress pathways influenced the fate of lymph node cells responding to ABC, implicating innate immune cells such as macrophages and plasmacytoid dendritic cells in the development of T-cell responses against the drug. IFN-I and IL-2 were necessary for CD8 + T-cell differentiation and ABC-induced adverse reactions. Conclusions This study unveils novel immune mechanisms driven by drug and host-related factors required forin vivoreactions and sheds light on potential biomarker and therapeutic targets for managing and preventing severe and life-threatening iDHR.

Immunology

A Discussion of Time Management Concepts and Time Constraint Equations for Multi-Rate Federation Executions

The High Level Architecture (HLA) is a simulation interoperability standard developed by the Simulation Interoperability Standards Organization (SISO) and published as the international standard IEEE 1516-2010 by the Institute for Electrical and Electronics Engineers (IEEE). HLA is a widely used standard for the development and execution of collaborative distributed simulations. HLA provides a number of Management Services to simulation developers: Federation, Declaration, Object, Ownership, Data Distribution, and Time. Of those services, Time Management Services is probably one of the least understood and least used. However, Time Management Services are critical to technical simulations like those created for space systems using the Space Reference Federation Object Model (SpaceFOM). Time Management can be used to insure data coherence and execution repeatability in distributed simulations. When combined with real time execution policies, Time Management is being used to support real time execution of mixed software and hardware in the loop integration, verification, and validation simulations for active space systems development. This paper starts by providing an overview of the HLA Time Management Services. This provides the background to discuss the challenges associated with Time Management and its use, starting with simple common rate frame scheduled simulations, then simple multi-rate simulations, and ending with complex mixed rate simulations. The authors then formulate the significant time constraint relationships between identified frame scheduling parameters. The intent of the paper is to provide a concise discussion of how to use Time Management in both simple cases and in more complex mixed frame rate federation executions.

Simulation Interoperability

A Discussion of Time Management Concepts and Time Constraint Equations for Multi-Rate Federation Executions

The High Level Architecture (HLA) is a simulation interoperability standard developed by the Simulation Interoperability Standards Organization (SISO) and published as the international standard IEEE 1516-2010 by the Institute for Electrical and Electronics Engineers (IEEE). HLA is a widely used standard for the development and execution of collaborative distributed simulations. HLA provides a number of Management Services to simulation developers: Federation, Declaration, Object, Ownership, Data Distribution, and Time. Of those services, Time Management Services is probably one of the least understood and least used. However, Time Management Services are critical to technical simulations like those created for space systems using the Space Reference Federation Object Model (SpaceFOM). Time Management can be used to insure data coherence and execution repeatability in distributed simulations. When combined with real time execution policies, Time Management is being used to support real time execution of mixed software and hardware in the loop integration, verification, and validation simulations for active space systems development. This paper starts by providing an overview of the HLA Time Management Services. This provides the background to discuss the challenges associated with Time Management and its use, starting with simple common rate frame scheduled simulations, then simple multi-rate simulations, and ending with complex mixed rate simulations. The authors then formulate the significant time constraint relationships between identified frame scheduling parameters. The intent of the paper is to provide a concise discussion of how to use Time Management in both simple cases and in more complex mixed frame rate federation executions.

Simulation Interoperability

Dynamic allostery in the peptide/MHC complex enables TCR neoantigen selectivity

Abstract The inherent antigen cross-reactivity of the T cell receptor (TCR) is balanced by high specificity. Surprisingly, TCR specificity often manifests in ways not easily interpreted from static structures. Here we show that TCR discrimination between an HLA-A*03:01 (HLA-A3)-restricted public neoantigen and its wild-type (WT) counterpart emerges from distinct motions within the HLA-A3 peptide binding groove that vary with the identity of the peptide’s first primary anchor. These motions create a dynamic gate that, in the presence of the WT peptide, impedes a large conformational change required for TCR binding. The neoantigen is insusceptible to this limiting dynamic, and, with the gate open, upon TCR binding the central tryptophan can transit underneath the peptide backbone to the opposing side of the HLA-A3 peptide binding groove. Our findings thus reveal a novel mechanism driving TCR specificity for a cancer neoantigen that is rooted in the dynamic and allosteric nature of peptide/MHC-I binding grooves, with implications for resolving long-standing and often confounding questions about T cell specificity.

Science & Technology - Other Topics

A funnel approach to enable analyses of epitope-specific human CD4 T cells specific for influenza and SARS-CoV-2

Protection against pathogens relies heavily on the adaptive immune response, whose key regulators are CD4 T cells. CD4 T cells, notable for their complex repertoire and functional potential, can most easily be dissected by identifying, quantifying, characterizing, and isolating epitope-specific cells. In the study reported here, we present a systematic and unbiased strategy that has enabled the identification of highly immunogenic peptide epitopes derived from influenza virus and SARS-CoV-2, presented by human HLA-DR proteins. Coupling the use of HLA-DR transgenic mice with infection and vaccination and highly sensitive epitope-specific cytokine ELISpot assays, we have narrowed the potential epitopes from 450 to 600 peptides to 5–15 peptides for each allele by an iterative process of elimination and selection, which we have termed a funnel approach. These epitopes have been validated in HLA-DR-typed human CD4 T cells directly ex vivo and enabled the derivation and implementation of HLA-DR peptide tetramers. Tetramer staining of human PBMCs enriched for CD4 T memory populations from healthy adult subjects, highlighted this approach as a sensitive and specific method for identifying novel epitopes, and subsequent CD4 T-cell responses to human viral infections.

CD4 T cell

High Level Architecture Distributed Space System Simulation for Simulation Interoperability Standards Organization Simulation Smackdown

Modeling and Simulation plays a very important role in mission design. It not only reduces design cost, but also prepares astronauts for their mission tasks. The SISO Smackdown is a simulation event that facilitates modeling and simulation in academia. The scenario of this year s Smackdown was to simulate a lunar base supply mission. The mission objective was to transfer Earth supply cargo to a lunar base supply depot and retrieve He-3 to take back to Earth. Federates for this scenario include the environment federate, Earth-Moon transfer vehicle, lunar shuttle, lunar rover, supply depot, mobile ISRU plant, exploratory hopper, and communication satellite. These federates were built by teams from all around the world, including teams from MIT, JSC, University of Alabama in Huntsville, University of Bordeaux from France, and University of Genoa from Italy. This paper focuses on the lunar shuttle federate, which was programmed by the USRP intern team from NASA JSC. The shuttle was responsible for provide transportation between lunar orbit and the lunar surface. The lunar shuttle federate was built using the NASA standard simulation package called Trick, and it was extended with HLA functions using TrickHLA. HLA functions of the lunar shuttle federate include sending and receiving interaction, publishing and subscribing attributes, and packing and unpacking fixed record data. The dynamics model of the lunar shuttle was modeled with three degrees of freedom, and the state propagation was obeying the law of two body dynamics. The descending trajectory of the lunar shuttle was designed by first defining a unique descending orbit in 2D space, and then defining a unique orbit in 3D space with the assumption of a non-rotating moon. Finally this assumption was taken away to define the initial position of the lunar shuttle so that it will start descending a second after it joins the execution. VPN software from SonicWall was used to connect federates with RTI during testing and the Smackdown event. HLA software from Pitch Technology and MAK Technology were used to edit and extend FOM and provide HLA services for federation execution. The SISO Smackdown event for 2011 was held in Boston, Massachusetts. The federation execution lasted for one hour, and the event was very successful in catching the attention of university students and faculties.

Li, Zuqun

SISO Space Reference FOM - Tools and Testing

The Simulation Interoperability Standards Organization (SISO) Space Reference Federation Object Model (SpaceFOM) version 1.0 is nearing completion. Earlier papers have described the use of the High Level Architecture (HLA) in Space simulation as well as technical aspects of the SpaceFOM. This paper takes a look at different SpaceFOM tools and how they were used during the development and testing of the standard.The first organizations to develop SpaceFOM-compliant federates for SpaceFOM development and testing were NASA's Johnson Space Center (JSC), the University of Calabria (UNICAL), and Pitch Technologies.JSC is one of NASA's lead centers for human space flight. Much of the core distributed simulation technology development, specifically associated with the SpaceFOM, is done by the NASA Exploration Systems Simulations (NExSyS) team. One of NASA's principal simulation development tools is the Trick Simulation Environment. NASA's NExSyS team has been modifying and using Trick and TrickHLA to help develop and test the SpaceFOM.The System Modeling And Simulation Hub Laboratory (SMASH-Lab) at UNICAL has developed the Simulation Exploration Experience (SEE) HLA Starter kit, that has been used by most SEE teams involved in the distributed simulation of a Moon base. It is particularly useful for the development of federates that are compatible with the SpaceFOM. The HLA Starter Kit is a Java based tool that provides a well-structured framework to simplify the formulation, generation, and execution of SpaceFOM-compliant federates.Pitch Technologies, a company specializing in distributed simulation, is utilizing a number of their existing HLA tools to support development and testing of the SpaceFOM. In addition to the existing tools, Pitch has developed a few SpaceFOM specific federates: Space Master for managing the initialization, execution and pacing of any SpaceFOM federation; EarthEnvironment, a simple Root Reference Publisher; and Space Monitor, a graphical tool for monitoring reference frames and physical entities.Early testing of the SpaceFOM was carried out in the SEE university outreach program, initiated in SISO. Students were given a subset of the FOM, that was later extended. Sample federates were developed and frameworks were developed or adapted to the early FOM versions.As drafts of the standard matured, testing was performed using federates from government, industry, and academia. By mixing federates developed by different teams the standard could be tested with respect to functional correctness, robustness and clarity.These frameworks and federates have been useful when testing and verifying the design of the standard. In addition to this, they have since formed a starting point for developing SpaceFOM-compliant federations in several projects, for example for NASA, ESA as well as SEE.

Möller, Björn

SpaceFOM: An Interoperability Standard for Space Systems Simulations

There is a long history of simulation supporting space systems development. This includes relatively simple parametric simulations to more complex trajectory simulations to large scale integrated vehicle simulation. One area of relatively recent development is in the area of distributed or interoperable simulation. Distributed simulation has been in wide use by the US military for years but is being used more broadly in the aerospace community. To support large scale distributed simulation, the military community has developed a number of standards to support a-priori interoperability between large collections of disparate simulations. For example, the IEEE 1516 High Level Architecture (HLA) and the Real-time Platform Reference Federation Object Model (RPR FOM). While HLA is suitable for space systems, there are a number of design decisions made in the development of the RPR FOM that prevent it from working well for space applications. In order to address these deficiencies, the Simulation Interoperability Standards Organization (SISO) developed a new HLA-based interoperability standard to support the needs of complex space systems. This standard is the Space Reference Federation Object Model (SpaceFOM). This paper presents an overview of the SpaceFOM including the fundamentals of the SpaceFOM, the key features of the SpaceFOM, and how the SpaceFOM supports large scale distributed simulation of complex space systems.

SpaceFOM

Study of Civil Markets for Heavy-Lift Airships

The civil markets for heavy lift airships (HLAs) were defined by first identifying areas of most likely application. The operational suitability of HLAs for the applications identified were then assessed. The operating economics of HLAs were established and the market size for HLA services estimated by comparing HLA operating and economic characteristics with those of competing modes. The sensitivities of the market size to HLA characteristics were evaluated and the number and sizes of the vehicles required to service the more promising markets were defined. Important characteristics for future HLAs are discussed that were derived from the study of each application, including operational requirements, features enhancing profitability, military compatibility, improved design requirements, approach to entry into service, and institutional implications for design and operation.

Mettam, P. J.

Generic multi-body formulation of heavy lift airship equations of motion

This paper describes the formulation of a comprehensive set of equations which describe the dynamic behavior of a generic heavy lift airship (HLA). They are being used in a digital computer simulation to investigate the response dynamics and flying qualities of HLAs operating with various payloads in a variety of operational environments. A key feature is the separate treatment of each component body making up the HLA. This allows the analyst to vary the configuration (e.g., number of lift-propulsion units, presence or absence of slung payload, etc.) without rewriting the equations. It further provides measures of key structural and control loads acting on the HLA and eases the task of modeling wind disturbances.

Ringland, R. F.