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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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS2016

Heart Rate Responses to Unaided Orion Side Hatch Egress in the Neutral Buoyancy Laboratory

NASA is developing the Orion capsule as a vehicle for transporting crewmembers to and from the International Space Station (ISS) and for future human space exploration missions. Orion and other commercial vehicles are designed to splash down in the ocean where nominally support personnel will assist crewmembers in egressing the vehicle. However, off-nominal scenarios will require crewmembers to egress the vehicle unaided, deploy survival equipment, and ingress a life raft. PURPOSE: To determine the heart rate (HR) responses to unaided Orion side hatch egress and raft ingress as a part of the NASA Crew Survival Engineering Team's evaluation of the PORT Orion mockup in the Neutral Buoyancy Laboratory (NBL). METHODS: Nineteen test subjects, including four astronauts (N=19, 14 males/5 females, 38.6+/-8.4 y, 174.4+/-9.6 cm, 75.7+/-13.1 kg), completed a graded maximal test on a cycle ergometer to determine VO2peak and HRpeak and were divided into five crews of four members each; one subject served on two crews. Each crew was required to deploy a life raft, egress the Orion vehicle from the side hatch, and ingress the life raft with two 8 kg emergency packs per crew. Each crew performed this activity one to three times; a total of ten full egresses were completed. Subjects wore a suit that was similar in form, mass, and function to the Modified Advanced Crew Escape Suit (MACES) including helmet, gloves, boots, supplemental O2 bottles, and a CO2-inflated life preserver (approx.18 kg); subjects began each trial seated supine in the PORT Orion mockup with seat belts and mockup O2 and communication connections and ended each trial with all four crewmembers inside the life raft. RESULTS: VO2peak was 40.8+/-6.8 mL/kg/min (3.1+/-0.7 L/min); HRpeak was 181+/-10 bpm. Total egress time across trials was 5.0+/-1.6 min (range: 2.8-8.0 min); all subjects were able to successfully complete all trials. Average maximum HR at activity start, at the hatch opening, in the water, and in the raft, was 108, 137, 147, and 153 bpm, respectively; these values corresponded to 59+/-10%, 73+/-8%, 82+/-3%, and 84+/-6% of HRpeak, respectively. The highest HRs were seen after raft ingress and ranged from 72-99% HRpeak. Across all trials, cumulative averages of 5.4, 3.0, 1.1, and 0.2 min were spent at HRs >60%, >70%, >80%, and >90% HRpeak, respectively. CONCLUSION: Unaided Orion side hatch egress in the NBL is a relatively short-duration activity that elicits a high HR response for several min. Although all crewmembers successfully completed this activity, additional factors such as high seas, poor visibility, an incapacitated crewmember, neurovestibular perturbation, and neuromuscular deconditioning characteristic of a true operational environment may increase the physiologic demand (or decrease crewmembers' physiologic capacity) of unaided Orion side hatch egress. Additionally, landing conditions may require the crewmembers to egress from the top hatch, which is expected to be even more physiologically demanding; this condition will be evaluated in subsequent collaborative testing with the NASA Crew Survival Engineering Team.

English, Kirk L.↗
NASA NTRS2008

Product Engineering Class in the Software Safety Risk Taxonomy for Building Safety-Critical Systems

When software safety requirements are imposed on legacy safety-critical systems, retrospective safety cases need to be formulated as part of recertifying the systems for further use and risks must be documented and managed to give confidence for reusing the systems. The SEJ Software Development Risk Taxonomy [4] focuses on general software development issues. It does not, however, cover all the safety risks. The Software Safety Risk Taxonomy [8] was developed which provides a construct for eliciting and categorizing software safety risks in a straightforward manner. In this paper, we present extended work on the taxonomy for safety that incorporates the additional issues inherent in the development and maintenance of safety-critical systems with software. An instrument called a Software Safety Risk Taxonomy Based Questionnaire (TBQ) is generated containing questions addressing each safety attribute in the Software Safety Risk Taxonomy. Software safety risks are surfaced using the new TBQ and then analyzed. In this paper we give the definitions for the specialized Product Engineering Class within the Software Safety Risk Taxonomy. At the end of the paper, we present the tool known as the 'Legacy Systems Risk Database Tool' that is used to collect and analyze the data required to show traceability to a particular safety standard

Hill, Janice↗
NASA NTRS2016

SC-228 Inclusion of DAA Warning Alert for TCAS Interoperability

This white paper summarizes NASA research results that have informed Special Committee 228 (SC-228) discussions and decisions regarding the inclusion of a warning-level alert within the detect and avoid (DAA) alerting structure for unmanned aircraft systems (UAS). For UAS, the removal of the pilot from onboard the aircraft has eliminated the ability of the ground-based pilot in command (PIC) to use out-the-window visual information to make judgments about a potential threat of a loss of well clear with another aircraft. As a result, the DAA traffic display will be the primary source of information that the PIC can use to execute the three primary well clear functions: 1) detect a potential loss of well clear, 2) determine a resolution maneuver, and 3) upload that maneuver to the aircraft via the ground control station (GCS). In addition, pilots are required to coordinate with air traffic control (ATC) prior to maneuvering off of their approved flight plan. In determining an appropriate resolution maneuver to avoid a loss of well clear, the PIC must decide both when and how to maneuver, and both the timeliness and the accuracy (i.e., correctness) of the maneuver are critical to reducing the likelihood and/or severity of a loss of well clear. Alerting information is one of three critical components of the DAA display, along with traffic information elements (e.g., relative heading, speed and altitude) and maneuver guidance. Alerting information and maneuver guidance, in particular, have been found to have a significant impact, both statistically and practically, on pilots' ability to avoid and minimize the severity of losses of well clear While all three display components are key to pilots performing the traffic avoidance task of remaining well clear, in general, alerting information provides crucial information about when a resolution maneuver is required while maneuver guidance assists the pilot in determining how best to maneuver. A fundamental task of the DAA alerting system is to provide critical timing information to the pilot about the potential for a loss of well clear with another aircraft. This is done by employing both temporal and spatial thresholds that indicate to the pilot the likelihood and imminence of a loss of well clear. The design of the DAA alerting thresholds is a balancing act between eliciting the desired pilot response in real loss of well clear threat events and reducing excessive, unnecessary, and/or uncoordinated UAS maneuvering within the air traffic environment; larger thresholds, both spatially and temporally, may increase the likelihood of a pilot avoiding a loss of well clear, but it can also increase the frequency of maneuvering - especially in cases where a maneuver is not actually needed to maintain well clear. A series of human in the loop (HITL) simulations have been conducted as part of NASA's Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) project. The purpose of these HITLs has been to provide empirical results in order to inform development of the minimum human-machine interface requirements for the DAA system. This white paper will present those results which provide evidence of a human performance benefit (in terms of response times and ability to remain well clear of other aircraft) of the DAA warning alert both with and without a collision avoidance system on board the aircraft.

TCAS interoperability↗
DOE OSTI2021

Design of Broadly Cross-Reactive M Protein–Based Group A Streptococcal Vaccines

Group A streptococcal infections are a significant cause of global morbidity and mortality. A leading vaccine candidate is the surface M protein, a major virulence determinant and protective Ag. An obstacle to the development of M protein–based vaccines is the >200 different M types defined by the N-terminal sequences that contain protective epitopes. Despite sequence variability, M proteins share coiled-coil structural motifs that bind host proteins required for virulence. In this study, we exploit this potential Achilles heel of conserved structure to predict cross-reactive M peptides that could serve as broadly protective vaccine Ags. Combining sequences with structural predictions, six heterologous M peptides in a sequence-related cluster were predicted to elicit cross-reactive Abs with the remaining five nonvaccine M types in the cluster. The six-valent vaccine elicited Abs in rabbits that reacted with all 11 M peptides in the cluster and functional opsonic Abs against vaccine and nonvaccine M types in the cluster. We next immunized mice with four sequence-unrelated M peptides predicted to contain different coiled-coil propensities and tested the antisera for cross-reactivity against 41 heterologous M peptides. Based on these results, we developed an improved algorithm to select cross-reactive peptide pairs using additional parameters of coiled-coil length and propensity. The revised algorithm accurately predicted cross-reactive Ab binding, improving the Matthews correlation coefficient from 0.42 to 0.74. These results form the basis for selecting the minimum number of N-terminal M peptides to include in potentially broadly efficacious multivalent vaccines that could impact the overall global burden of group A streptococcal diseases.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2014

Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10‐week‐old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger‐NYU nose‐only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4‐week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe response to the lunar dust insult at higher levels. Pathways of interests that have been identified in all exposed samples include oxidative stress response, mitochondrial dysfunction, fibrosis, epithelial healing, TGF-Beta signaling, and extracellular matrix remodeling. Several biological processes related to cell migration, cellular proliferation, and eye development were also identified to be altered by exposure to lunar dust. Our preliminary results suggest that even a chronic insult of lunar dust as low as 20 mg/m(exp 3) elicits a molecular response in cornea tissue. Lunar dust on the surface of the moon would have the added properties of ionization and activation potentially leading to further damage to the cornea and greater sensitivity to any other environmental insult such as exposure to radiation. Additional studies are required to fully assess the risk of vision impairment and the mechanistic responses initiated in cornea exposed to lunar dust as well as the potential for long‐term effects to astronaut health

Theriot, C. A.↗
NASA NTRS1992

From a lunar outpost to Mars - Science, policy and the U.S. Space Exploration Initiative

The technological developments required for the Space Exploration Initiative (SEI) objectives are discussed in terms of scientific investigation and present U.S. space policy. The results of the 90-Day Study are listed which include explicit suggestions for the successful exploration of the moon and Mars. The Outreach/Synthesis program is described which provides four methods for eliciting ideas, technologies, and research venues for lunar and Martian missions. The results of the studies include 5 scientific objectives such as the relationship between the sun, planetary atmospheres, and climate. The protection of human life from potential extraterrestrial hazards such as radiation is also found to be a key objective of SEI as are the theoretical and practical issues of scientific research.

Pilcher, Carl B.↗
NASA NTRS1992

Concepts and application of dynamic separation for agility and super-maneuverability of aircraft: An assessment

Aims for improvement of fighter aircraft pursued by the unsteady flow community are high agility (the ability of the aircraft to make close turns in a low-speed regime) and super maneuverability (the ability of the aircraft to operate at high angles of attack in a post stall regime during quick maneuvers in a more extended speed range). High agility requires high lift coefficients at low speeds in a dynamic situation and this requirement can be met by dynamically forced separation or by quasistatic stall control. The competing methods will be assessed based on the known physics. Maneuvering into the post stall regime also involves dynamic separation but because even fast maneuvers involving the entire aircraft are 'aerodynamically slow' the resulting dynamic vortex structures should be considered 'elicited' rather than 'forced.' More work seems to be needed in this area of elicited dynamic separation.

Freymuth, Peter↗
NASA NTRS2003

Cross-axis adaptation of torsional components in the yaw-axis vestibulo-ocular reflex

The three pairs of semicircular canals within the labyrinth are not perfectly aligned with the pulling directions of the six extraocular muscles. Therefore, for a given head movement, the vestibulo-ocular reflex (VOR) depends upon central neural mechanisms that couple the canals to the muscles with the appropriate functional gains in order to generate a response that rotates the eye the correct amount and around the correct axis. A consequence of these neural connections is a cross-axis adaptive capability, which can be stimulated experimentally when head rotation is around one axis and visual motion about another. From this visual-vestibular conflict the brain infers that the slow-phase eye movement is rotating around the wrong axis. We explored the capability of human cross-axis adaptation, using a short-term training paradigm, to determine if torsional eye movements could be elicited by yaw (horizontal) head rotation (where torsion is normally inappropriate). We applied yaw sinusoidal head rotation (+/-10 degrees, 0.33 Hz) and measured eye movement responses in the dark, and before and after adaptation. The adaptation paradigm lasted 45-60 min, and consisted of the identical head motion, coupled with a moving visual scene that required one of several types of eye movements: (1) torsion alone (-Roll); (2) horizontal/torsional, head right/CW torsion (Yaw-Roll); (3) horizontal/torsional, head right/CCW torsion (Yaw+Roll); (4) horizontal, vertical, torsional combined (Yaw+Pitch-Roll); and (5) horizontal and vertical together (Yaw+Pitch). The largest and most significant changes in torsional amplitude occurred in the Yaw-Roll and Yaw+Roll conditions. We conclude that short-term, cross-axis adaptation of torsion is possible but constrained by the complexity of the adaptation task: smaller torsional components are produced if more than one cross-coupling component is required. In contrast, vertical cross-axis components can be easily trained to occur with yaw head movements.

Non-NASA Center↗
DOE OSTI2021

Machine Learning for Automated Weld Quality Monitoring and Control (CRADA 461)

The emergence of Artificial Intelligence (AI) and Machine Learning (ML) methods may provide an alternative pathway to elicit the desired process-structure-property relationship. To achieve such relationship at an accelerated pace the use of data driven machine learning techniques are employed. This CRADA investigates the use and effectiveness of applying AI/ML techniques to a large dataset with the intention of creating a data-driven model that will predict processing parameters required to join lightweight materials at optimal performance.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS1998

Neural learning rules for the vestibulo-ocular reflex

Mechanisms for the induction of motor learning in the vestibulo-ocular reflex (VOR) were evaluated by recording the patterns of neural activity elicited in the cerebellum by a range of stimuli that induce learning. Patterns of climbing-fiber, vestibular, and Purkinje cell simple-spike signals were examined during sinusoidal head movement paired with visual image movement at stimulus frequencies from 0.5 to 10 Hz. A comparison of simple-spike and vestibular signals contained the information required to guide learning only at low stimulus frequencies, and a comparison of climbing-fiber and simple-spike signals contained the information required to guide learning only at high stimulus frequencies. Learning could be guided by comparison of climbing-fiber and vestibular signals at all stimulus frequencies tested, but only if climbing fiber responses were compared with the vestibular signals present 100 msec earlier. Computational analysis demonstrated that this conclusion is valid even if there is a broad range of vestibular signals at the site of plasticity. Simulations also indicated that the comparison of vestibular and climbing-fiber signals across the 100 msec delay must be implemented by a subcellular "eligibility" trace rather than by neural circuits that delay the vestibular inputs to the site of plasticity. The results suggest two alternative accounts of learning in the VOR. Either there are multiple mechanisms of learning that use different combinations of neural signals to drive plasticity, or there is a single mechanism tuned to climbing-fiber activity that follows activity in vestibular pathways by approximately 100 msec.

NASA Discipline Neuroscience↗
DOE OSTI2022

Assessing Community Preferences Regarding Solar Development

Preparing a plan regarding solar development in your community requires bringing together people from a variety of backgrounds and perspectives, who often have strong feelings and preferences about the amount and location of local solar PV projects developed in their community. The planning process should be designed in an inclusive way, where meaningful community engagement is prioritized. With a topic such as solar development, which can elicit strong reactions among community members, proactive community engagement that is perceived as fair will likely lead to more favorable outcomes. Whether your community hosts large tracts of forest, brownfields, residential neighborhoods, and/or large buildings and parking lots, there are a variety of ways community members might envision growth of solar energy. The engagement process can help clarify how and where solar is preferred, so that local government can respond to future solar development requests or to initiate solar projects that are preferred by the community.

14 SOLAR ENERGY↗
NASA NTRS2002

Supercomputing 2002: NAS Demo Abstracts

The hyperwall is a new concept in visual supercomputing, conceived and developed by the NAS Exploratory Computing Group. The hyperwall will allow simultaneous and coordinated visualization and interaction of an array of processes, such as a the computations of a parameter study or the parallel evolutions of a genetic algorithm population. Making over 65 million pixels available to the user, the hyperwall will enable and elicit qualitatively new ways of leveraging computers to accomplish science. It is currently still unclear whether we will be able to transport the hyperwall to SC02. The crucial display frame still has not been completed by the metal fabrication shop, although they promised an August delivery. Also, we are still working the fragile node issue, which may require transplantation of the compute nodes from the present 2U cases into 3U cases. This modification will increase the present 3-rack configuration to 5 racks.

Parks, John↗
DOE OSTI2023

A Systematic Study to Determine 5G Baseline Performance for Scientific Computing

The fifth-generation (5G) cellular networks envisions achieving higher data rates, improved connectivity, reduced latency, and better quality of service (QoS) than the fourthgeneration (4G) cellular networks. Such improved performance can be utilized to address the challenges in applications such as electricity generation in power systems. The traditional power grids responsible for electricity generation suffer from drawbacks such as life-threatening blackout crises, and energy storage proliferation as they are not robust to extreme climatic conditions. A recent study proposed the idea of extending the capabilities of advanced wireless technologies such as the current 5G to develop a robust, energy-efficient, and secure smart grids. However there are two main challenges associated with the integration of power systems and wireless technologies. First, it is imperative to understand the architecture and the enabling technologies of 5G to ensure that the performance requirements of the smart grids are met. Second, an end-to-end testbed is required to determine if the performance requirements are met by estimating the 5G characteristics such as latency, and throughput. Our proposed alleviates the aforementioned concerns in the following manner. To begin with, a systematic study of the 5G architecture including both the StandAlone (SA) and Non-Standalone (NSA) operations is presented. Furthermore, a detailed survey of the possible 5G enabling technologies is elicited. In addition to these, an end-toend testbed that can estimate the 5G characteristics is explained in detail with appropriate preliminary results.

5G, 5G Communication↗
DOE OSTI2020

The Technical and Economic Potential of the H2@Scale Hydrogen Concept within the United States

The U.S. energy system is evolving as society and technologies change. Renewable electricity generation - especially from wind and solar - is growing rapidly, and alternative energy sources are being developed and implemented across the residential, commercial, transportation, and industrial sectors to take advantage of their cost, security, and health benefits. Systemic changes present numerous challenges to grid resiliency and energy affordability, creating a need for synergistic solutions that satisfy multiple applications while yielding system-wide cost and emissions benefits. One such solution is an integrated hydrogen energy system. This is the focus of H2@Scale - a U.S. Department of Energy (DOE) initiative led by the Office of Energy Efficiency and Renewable Energy’s Hydrogen and Fuel Technologies Office. H2@Scale brings together stakeholders to advance affordable hydrogen production, transport, storage, and utilization in multiple energy sectors. The H2@Scale concept involves hydrogen as an energy intermediate. Hydrogen can be produced from various conventional and renewable energy sources including as a responsive load on the electric grid. Hydrogen has many current applications and many more potential applications, such as energy for transportation - used directly in fuel cell electric vehicles (FCEVs), as a feedstock for synthetic fuels, and to upgrade oil and biomass - feedstock for industry (e.g., for ammonia production, metals refining, and other end uses), heat for industry and buildings, and electricity storage. Owing to its flexibility and fungibility, a hydrogen intermediate could link energy sources that have surplus availability to markets that require energy or chemical feedstocks, benefiting both. This document builds upon a growing body of analyses of hydrogen as an energy intermediate by reporting the results from our initial analysis of the potential impacts of the H2@Scale vision by the mid-21 st century for the 48 contiguous U.S. states. Previous estimates have been based on expert elicitation and focused on hydrogen demands. We build upon them, first, by estimating hydrogen’s serviceable consumption potential for possible hydrogen applications and the technical potential for producing hydrogen from various resources. We define the serviceable consumption potential as the quantity of hydrogen that would be consumed to serve the portion of the market that could be captured without considering economics (i.e., if the price of hydrogen were $0/kg over an extended period); thus, it can be considered an upper bound for the size of the market. We define the technical potential as the resource potential constrained by real-world geography and system performance, but not by economics. We then compare the cumulative serviceable consumption potential with the technical potential of a number of possible sources. Second, we estimate economic potential: the quantity of hydrogen at an equilibrium price at which suppliers are willing to sell and consumers are willing to buy the same quantity of hydrogen. We believe this method provides a deeper understanding than was available in the previous analyses. We develop economic potentials for multiple scenarios across various market and technology-advancement assumptions.

08 HYDROGEN↗
NASA NTRS2014

Probabilistic 21st and 22nd Century Sea-Level Projections at a Global Network of Tide-Gauge Sites

Sea-level rise due to both climate change and non-climatic factors threatens coastal settlements, infrastructure, and ecosystems. Projections of mean global sea-level (GSL) rise provide insufficient information to plan adaptive responses; local decisions require local projections that accommodate different risk tolerances and time frames and that can be linked to storm surge projections. Here we present a global set of local sea-level (LSL) projections to inform decisions on timescales ranging from the coming decades through the 22nd century. We provide complete probability distributions, informed by a combination of expert community assessment, expert elicitation, and process modeling. Between the years 2000 and 2100, we project a very likely (90% probability) GSL rise of 0.5–1.2 m under representative concentration pathway (RCP) 8.5, 0.4–0.9 m under RCP 4.5, and 0.3–0.8 m under RCP 2.6. Site-to-site differences in LSL projections are due to varying non-climatic background uplift or subsidence, oceanographic effects, and spatially variable responses of the geoid and the lithosphere to shrinking land ice. The Antarctic ice sheet (AIS) constitutes a growing share of variance in GSL and LSL projections. In the global average and at many locations, it is the dominant source of variance in late 21st century projections, though at some sites oceanographic processes contribute the largest share throughout the century. LSL rise dramatically reshapes flood risk, greatly increasing the expected number of “1-in-10” and “1-in-100” year events.

sea level↗
NASA NTRS1997

Towards a Methodology for Identifying Program Constraints During Requirements Analysis

Requirements analysis is the activity that involves determining the needs of the customer, identifying the services that the software system should provide and understanding the constraints on the solution. The result of this activity is a natural language document, typically referred to as the requirements definition document. Some of the problems that exist in defining requirements in large scale software projects includes synthesizing knowledge from various domain experts and communicating this information across multiple levels of personnel. One approach that addresses part of this problem is called context monitoring and involves identifying the properties of and relationships between objects that the system will manipulate. This paper examines several software development methodologies, discusses the support that each provide for eliciting such information from experts and specifying the information, and suggests refinements to these methodologies.

Romo, Lilly↗
NASA NTRS2004

Transitioning from Software Requirements Models to Design Models

The Scenario Creation and Simulation Process (SCASP) includes the following steps: 1) Write Requirements; 2) Write Use Cases; 3) Prioritize Use Cases; 4) Write Nominal Scenarios; 5) Identify Relationships; 6) Refine/Generalize Scenarios; 7) Transform to State Machines. SCASP provides thorough simulation of use cases before design/implementation, resulting in: 1) Reduced cost; 2) Fewer misunderstandings; 3) Reuse of executable form of use cases. SCASP gives systematic guidelines on how to 1) Separate concerns in use case descriptions; 2) Elicit non-nominal scenarios (alternatives, exceptions, concurrent scenarios, etc.); 3) Transform those scenarios automatically into a set of concurrent state machines; 4) Execute those state machines, i.e., scenario simulation.

Whittle, Jon↗
DOE OSTI2024

Priming antibody responses to the fusion peptide in rhesus macaques

Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

60 APPLIED LIFE SCIENCES↗