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DOE OSTI2024

CD46-Targeted Theranostics for PET and 225 Ac-Radiopharmaceutical Therapy of Multiple Myeloma

Multiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [ 89 Zr]Zr-DFO-YS5 for imaging and [ 225 Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer. These prior studies suggested the feasibility of the CD46 antigen as a theranostic target in multiple myeloma. Herein, we validate [ 89 Zr]Zr-DFO-YS5 for immunoPET imaging and [ 225 Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of multiple myeloma in murine models. In vitro saturation binding was performed using the CD46 expressing MM.1S multiple myeloma cell line. ImmunoPET imaging using [ 89 Zr]Zr-DFO-YS5 was performed in immunodeficient (NSG) mice bearing subcutaneous and systemic multiple myeloma xenografts. For radioligand therapy, [ 225 Ac]Ac-DOTA-YS5 was prepared, and both dose escalation and fractionated dose treatment studies were performed in mice bearing MM1.S-Luc systemic xenografts. Tumor burden was analyzed using BLI, and body weight and overall survival were recorded to assess antitumor effect and toxicity. [ 89 Zr]Zr-DFO-YS5 demonstrated high affinity for CD46 expressing MM.1S multiple myeloma cells (K d = 16.3 nmol/L). In vitro assays in multiple myeloma cell lines demonstrated high binding, and bioinformatics analysis of human multiple myeloma samples revealed high CD46 expression. [ 89 Zr]Zr-DFO-YS5 PET/CT specifically detected multiple myeloma lesions in a variety of models, with low uptake in controls, including CD46 knockout (KO) mice or multiple myeloma mice using a nontargeted antibody. In the MM.1S systemic model, localization of uptake on PET imaging correlated well with the luciferase expression from tumor cells. A treatment study using [ 225 Ac]Ac-DOTA-YS5 in the MM.1S systemic model demonstrated a clear tumor volume and survival benefit in the treated groups. Our study showed that the CD46-targeted probe [ 89 Zr]Zr-DFO-YS5 can successfully image CD46-expressing multiple myeloma xenografts in murine models, and [ 225 Ac]Ac-DOTA-YS5 can effectively inhibit the growth of multiple myeloma. These results demonstrate that CD46 is a promising theranostic target for multiple myeloma, with the potential for clinical translation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Efficient DNA sequence compression with neural networks

Abstract Background The increasing production of genomic data has led to an intensified need for models that can cope efficiently with the lossless compression of DNA sequences. Important applications include long-term storage and compression-based data analysis. In the literature, only a few recent articles propose the use of neural networks for DNA sequence compression. However, they fall short when compared with specific DNA compression tools, such as GeCo2. This limitation is due to the absence of models specifically designed for DNA sequences. In this work, we combine the power of neural networks with specific DNA models. For this purpose, we created GeCo3, a new genomic sequence compressor that uses neural networks for mixing multiple context and substitution-tolerant context models. Findings We benchmark GeCo3 as a reference-free DNA compressor in 5 datasets, including a balanced and comprehensive dataset of DNA sequences, the Y-chromosome and human mitogenome, 2 compilations of archaeal and virus genomes, 4 whole genomes, and 2 collections of FASTQ data of a human virome and ancient DNA. GeCo3 achieves a solid improvement in compression over the previous version (GeCo2) of $2.4\%$, $7.1\%$, $6.1\%$, $5.8\%$, and $6.0\%$, respectively. To test its performance as a reference-based DNA compressor, we benchmark GeCo3 in 4 datasets constituted by the pairwise compression of the chromosomes of the genomes of several primates. GeCo3 improves the compression in $12.4\%$, $11.7\%$, $10.8\%$, and $10.1\%$ over the state of the art. The cost of this compression improvement is some additional computational time (1.7–3 times slower than GeCo2). The RAM use is constant, and the tool scales efficiently, independently of the sequence size. Overall, these values outperform the state of the art. Conclusions GeCo3 is a genomic sequence compressor with a neural network mixing approach that provides additional gains over top specific genomic compressors. The proposed mixing method is portable, requiring only the probabilities of the models as inputs, providing easy adaptation to other data compressors or compression-based data analysis tools. GeCo3 is released under GPLv3 and is available for free download at https://github.com/cobilab/geco3.

Silva, Milton↗

DOE OSTI2020

Energy Impact of Connected and Automated Vehicle Technologies. Final report

The overarching goal of this project is to understand the potential impact of connected and automated vehicles. The goal was achieved through data collection, model development, algorithm designs, simulations, and limited field tests. The main outcomes from this project include: (1) we collected energy consumption and GPS data from 500 vehicles over one year, with a total mileage of 8 million miles; (2) Based on the collected data and other datasets collected at the University of Michigan, we developed a calibrated Ann Arbor model in Polaris (model developed by ANL), and the fuel economy accuracy was found to be around 3.9% by comparison with field collected data; (3) An open-source SUMO model of Ann Arbor was developed; (4) Eco-Routing algorithms in Ann Arbor using the SUMO model shows 6% fuel saving potential; (5) Experiments conducted at the Mcity test facility shows that human drivers roughly follow the Eco-driving suggestions roughly 70% of the time; (6) Based in the Ann Arbor travel patterns, we found that each shared automated vehicle can replace around 4 individually owned vehicles; and (7) Adaptive Traffic Signal Control Algorithm developed through this project has been validated both in simulations and preliminary test results. For connected and automated vehicles, on average the performance is 13% delay reduction, and 10% fuel reduction. While connected and automated vehicles are in their early stage of deployment, the results from this project confirm that there is significant potential for energy saving if the technologies are developed and used properly. The three main technologies studied in this project include eco-routing, shared autonomous rides, and adaptive traffic signal controls. The data collected and model developed through the project can be used to study many other connected and automated vehicle technologies.

02 PETROLEUM↗

DOE OSTI2022

Behavioral and Population Data-Driven Distribution System Load Modeling

Distribution system residential load modeling and analysis for different geographic areas within a utility or an independent system operator territory are critical for enabling small-scale, aggregated distributed energy resources to participate in grid services under Federal Energy Regulatory Commission Order No. 2222 [1]. In this study, we develop a methodology of modeling residential load profiles in different geographic areas with a focus on human behavior impact. First, we construct a behavior-based load profile model leveraging state-of-the-art appliance models. We simulate human activity and occupancy using Markov chain Monte Carlo methods calibrated with the American Time Use Survey data set. Second, we link our model with cleaned Current Population Survey data from the U.S. Census Bureau. Finally, we populate two sets of 500 households using California and Texas census data, respectively, to perform an initial analysis of the load in different geographic areas with various group features (e.g., different income levels). To distinguish the effect of population behavior differences on aggregated load, we simulate load profiles for both sets assuming fixed physical household parameters and weather data. Analysis shows that average daily load profiles vary significantly by income and income dependency varies by locality.

American Time Use Survey↗

NASA NTRS1981

Multivariable closed loop control analysis and synthesis for complex flight systems

A flight control system analysis and synthesis method is presented that is intended to be especially suitable for application to vehicles exhibiting complex dynamic characteristics. For such vehicles quantitative handling qualities specifications are not usually available. Howver, handling qualities objectives are specifically introduced in this method via the hypothesis of correlation between pilot ratings and the objective function of an optimal control model of the human pilot. Further, since augmentation and pilot operate in parallel, simultaneous determination of the augmentation and pilot model gains is required. Desirable augmented dynamics are obtained for a variety of complex systems and the method is experimentally verified in the case of simple pilot damper gain selection for optimum pitch tracking performance.

Schmidt, D. K.↗

NASA NTRS1982

An experimental study of human pilot's scanning behavior

The scanning behavior and the control behavior of the pilot who manually controls the two-variable system, which is the most basic one of multi-variable systems are investigated. Two control tasks which simulate the actual airplane attitude and airspeed control were set up. In order to simulate the change of the situation where the pilot is placed, such as changes of flight phase, mission and others, the subject was requested to vary the weightings, as his control strategy, upon each task. Changes of human control dynamics and his canning properties caused by the modification of the situation were investigated. By making use of the experimental results, the optimal model of the control behavior and the scanning behavior of the pilot in the two-variable system is proposed from the standpoint of making the performance index minimal.

Washizu, K.↗

NASA NTRS1991

Bioregenerative life support - The initial CELSS reference configuration

The next major step in the development of an operational Controlled Ecological Life-Support System (CELSS) is the creation of a human-rated ground-based demonstrator able to constitute a CELSS's proof-of-concept. The reference configuration recently devised for such a ground facility by NASA will furnish a common reference to all investigators in the field, thereby facilitating performance comparisons among candidate subsystems and clarifying system-level modeling. A detailed NASA reference CELSS flowcharting is presented.

Rummel, John D.↗

NASA NTRS2002

Stimulus information contaminates summation tests of independent neural representations of features

Many models of visual processing assume that visual information is analyzed into separable and independent neural codes, or features. A common psychophysical test of independent features is known as a summation study, which measures performance in a detection, discrimination, or visual search task as the number of proposed features increases. Improvement in human performance with increasing number of available features is typically attributed to the summation, or combination, of information across independent neural coding of the features. In many instances, however, increasing the number of available features also increases the stimulus information in the task, as assessed by an optimal observer that does not include the independent neural codes. In a visual search task with spatial frequency and orientation as the component features, a particular set of stimuli were chosen so that all searches had equivalent stimulus information, regardless of the number of features. In this case, human performance did not improve with increasing number of features, implying that the improvement observed with additional features may be due to stimulus information and not the combination across independent features.

NASA Discipline Space Human Factors↗

NASA NTRS2014

High-Power Hall Propulsion Development at NASA Glenn Research Center

The NASA Office of the Chief Technologist Game Changing Division is sponsoring the development and testing of enabling technologies to achieve efficient and reliable human space exploration. High-power solar electric propulsion has been proposed by NASA's Human Exploration Framework Team as an option to achieve these ambitious missions to near Earth objects. NASA Glenn Research Center (NASA Glenn) is leading the development of mission concepts for a solar electric propulsion Technical Demonstration Mission. The mission concepts are highlighted in this paper but are detailed in a companion paper. There are also multiple projects that are developing technologies to support a demonstration mission and are also extensible to NASA's goals of human space exploration. Specifically, the In-Space Propulsion technology development project at NASA Glenn has a number of tasks related to high-power Hall thrusters including performance evaluation of existing Hall thrusters; performing detailed internal discharge chamber, near-field, and far-field plasma measurements; performing detailed physics-based modeling with the NASA Jet Propulsion Laboratory's Hall2De code; performing thermal and structural modeling; and developing high-power efficient discharge modules for power processing. This paper summarizes the various technology development tasks and progress made to date

Kamhawi, Hani↗

NASA NTRS2014

Mars Atmosphere Resource Verification INsitu (MARVIN) - In Situ Resource Demonstration for the Mars 2020 Mission

The making of oxygen from resources in the Martian atmosphere, known as In Situ Resource Utilization (ISRU), has the potential to provide substantial benefits for future robotic and human exploration. In particular, the ability to produce oxygen on Mars for use in propulsion, life support, and power systems can provide significant mission benefits such as a reducing launch mass, lander size, and mission and crew risk. To advance ISRU for possible incorporation into future human missions to Mars, NASA proposed including an ISRU instrument on the Mars 2020 rover mission, through an announcement of opportunity (AO). The purpose of the the Mars Atmosphere Resource Verification INsitu or (MARVIN) instrument is to provide the first demonstration on Mars of oxygen production from acquired and stored Martian atmospheric carbon dioxide, as well as take measurements of atmospheric pressure and temperature, and of suspended dust particle sizes and amounts entrained in collected atmosphere gases at different times of the Mars day and year. The hardware performance and environmental data obtained will be critical for future ISRU systems that will reduce the mass of propellants and other consumables launched from Earth for robotic and human exploration, for better understanding of Mars dust and mitigation techniques to improve crew safety, and to help further define Mars global circulation models and better understand the regional atmospheric dynamics on Mars. The technologies selected for MARVIN are also scalable for future robotic sample return and human missions to Mars using ISRU.

Sanders, Gerald B.↗

NASA NTRS2011

Integration Process for the Habitat Demonstration Unit

The Habitat Demonstration Unit (HDU) is an experimental exploration habitat technology and architecture test platform designed for analog demonstration activities. The HDU previously served as a test bed for testing technologies and sub-systems in a terrestrial surface environment. in 2010 in the Pressurized Excursion Module (PEM) configuration. Due to the amount of work involved to make the HDU project successful, the HDU project has required a team to integrate a variety of contributions from NASA centers and outside collaborators The size of the team and number of systems involved With the HDU makes Integration a complicated process. However, because the HDU shell manufacturing is complete, the team has a head start on FY--11 integration activities and can focus on integrating upgrades to existing systems as well as integrating new additions. To complete the development of the FY-11 HDU from conception to rollout for operations in July 2011, a cohesive integration strategy has been developed to integrate the various systems of HDU and the payloads. The highlighted HDU work for FY-11 will focus on performing upgrades to the PEM configuration, adding the X-Hab as a second level, adding a new porch providing the astronauts a larger work area outside the HDU for EVA preparations, and adding a Hygiene module. Together these upgrades result in a prototype configuration of the Deep Space Habitat (DSH), an element under evaluation by NASA's Human Exploration Framework Team (HEFT) Scheduled activates include early fit-checks and the utilization of a Habitat avionics test bed prior to installation into HDU. A coordinated effort to utilize modeling and simulation systems has aided in design and integration concept development. Modeling tools have been effective in hardware systems layout, cable routing, sub-system interface length estimation and human factors analysis. Decision processes on integration and use of all new subsystems will be defined early in the project to maximize the efficiency of both integration and field operations. In addition a series of tailored design reviews are utilized to quickly define the systems and their integration into the DSH configuration. These processes are necessary to ensure activities, such as partially reversing integration of the X-Hab second story of the HDU and deploying and stowing the new work porch for transportation to the JSC Rock Yard and to the Arizona Black Point Lava Flow Site are performed with minimal or no complications. In addition, incremental test operations leading up to an Integrated systems test allows for an orderly systems test program. For FY-11 activities, the HDU DSH will act as a laboratory utilizing a new X-Hab inflatable second floor with crew habitation features. In addition to the day to day operations involving maintenance of the HDU and exploring the surrounding terrain, testing and optimizing the use of the new X-Hab, work porch, Hygiene Module, and other sub-system enhancements will be the focus of the FY-11 test objectives. The HDU team requires a successful integration strategy using a variety of tools and approaches to prepare the DSH for these test objectives. In a challenging environment where the prototyping influences the system design, as well as Vice versa, results of the HDU DSH field tests will influence future designs of habitat systems.

Gill, Tracy↗

NASA NTRS1994

Rule based design of conceptual models for formative evaluation

A Human-Computer Interface (HCI) Prototyping Environment with embedded evaluation capability has been investigated. This environment will be valuable in developing and refining HCI standards and evaluating program/project interface development, especially Space Station Freedom on-board displays for payload operations. This environment, which allows for rapid prototyping and evaluation of graphical interfaces, includes the following four components: (1) a HCI development tool, (2) a low fidelity simulator development tool, (3) a dynamic, interactive interface between the HCI and the simulator, and (4) an embedded evaluator that evaluates the adequacy of a HCI based on a user's performance. The embedded evaluation tool collects data while the user is interacting with the system and evaluates the adequacy of an interface based on a user's performance. This paper describes the design of conceptual models for the embedded evaluation system using a rule-based approach.

Moore, Loretta A.↗

NASA NTRS1994

Rule based design of conceptual models for formative evaluation

A Human-Computer Interface (HCI) Prototyping Environment with embedded evaluation capability has been investigated. This environment will be valuable in developing and refining HCI standards and evaluating program/project interface development, especially Space Station Freedom on-board displays for payload operations. This environment, which allows for rapid prototyping and evaluation of graphical interfaces, includes the following four components: (1) a HCI development tool; (2) a low fidelity simulator development tool; (3) a dynamic, interactive interface between the HCI and the simulator; and (4) an embedded evaluator that evaluates the adequacy of a HCI based on a user's performance. The embedded evaluation tool collects data while the user is interacting with the system and evaluates the adequacy of an interface based on a user's performance. This paper describes the design of conceptual models for the embedded evaluation system using a rule-based approach.

Moore, Loretta A.↗

NASA NTRS2008

Analysis of Logistics in Support of a Human Lunar Outpost

Strategic level analysis of the integrated behavior of lunar transportation system and lunar surface system architecture options is performed to inform NASA Constellation Program senior management on the benefit, viability, affordability, and robustness of system design choices. This paper presents an overview of the approach used to perform the campaign (strategic) analysis, with an emphasis on the logistics modeling and the impacts of logistics resupply on campaign behavior. An overview of deterministic and probabilistic analysis approaches is provided, with a discussion of the importance of each approach to understanding the integrated system behavior. The logistics required to support lunar surface habitation are analyzed from both 'macro-logistics' and 'micro-logistics' perspectives, where macro-logistics focuses on the delivery of goods to a destination and micro-logistics focuses on local handling of re-supply goods at a destination. An example campaign is provided to tie the theories of campaign analysis to results generation capabilities.

Cirillo, William↗

NASA NTRS2001

Cockpit Adaptive Automation and Pilot Performance

The introduction of high-level automated systems in the aircraft cockpit has provided several benefits, e.g., new capabilities, enhanced operational efficiency, and reduced crew workload. At the same time, conventional 'static' automation has sometimes degraded human operator monitoring performance, increased workload, and reduced situation awareness. Adaptive automation represents an alternative to static automation. In this approach, task allocation between human operators and computer systems is flexible and context-dependent rather than static. Adaptive automation, or adaptive task allocation, is thought to provide for regulation of operator workload and performance, while preserving the benefits of static automation. In previous research we have reported beneficial effects of adaptive automation on the performance of both pilots and non-pilots of flight-related tasks. For adaptive systems to be viable, however, such benefits need to be examined jointly in the context of a single set of tasks. The studies carried out under this project evaluated a systematic method for combining different forms of adaptive automation. A model for effective combination of different forms of adaptive automation, based on matching adaptation to operator workload was proposed and tested. The model was evaluated in studies using IFR-rated pilots flying a general-aviation simulator. Performance, subjective, and physiological (heart rate variability, eye scan-paths) measures of workload were recorded. The studies compared workload-based adaptation to to non-adaptive control conditions and found evidence for systematic benefits of adaptive automation. The research provides an empirical basis for evaluating the effectiveness of adaptive automation in the cockpit. The results contribute to the development of design principles and guidelines for the implementation of adaptive automation in the cockpit, particularly in general aviation, and in other human-machine systems. Project goals were met or exceeded. The results of the research extended knowledge of automation-related performance decrements in pilots and demonstrated the positive effects of adaptive task allocation. In addition, several practical implications for cockpit automation design were drawn from the research conducted. A total of 12 articles deriving from the project were published.

Parasuraman, Raja↗

DOE OSTI2025

Foundation Models for Zero-Shot Segmentation of Scientific Images without AI-Ready Data

Zero-shot and prompt-based models have excelled at visual reasoning tasks by leveraging large-scale natural image corpora, but they often fail on sparse and domain-specific scientific image data. We introduce Zenesis, a no-code interactive computer vision platform designed to reduce data readiness bottlenecks in scientific imaging workflows. Zenesis integrates lightweight multimodal adaptation for zero-shot inference on raw scientific data, human-in-the-loop refinement, and heuristic-based temporal enhancement. We validate our approach on Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) datasets of catalyst-loaded membranes. Zenesis outperforms baselines, achieving an average accuracy of 0.947, Intersection over Union (IoU) of 0.858, and Dice score of 0.923 on amorphous catalyst samples; and 0.987 accuracy, 0.857 IoU, and 0.923 Dice on crystalline samples. These results represent a significant performance gain over conventional methods such as Otsu thresholding and standalone models like the Segment Anything Model (SAM). Zenesis enables effective image segmentation in domains where annotated datasets are limited, offering a scalable solution for scientific discovery.

Mukherjee, Shubhabrata↗

NASA NTRS2012

Cognitive Systems Modeling and Analysis of Command and Control Systems

Military operations, counter-terrorism operations and emergency response often oblige operators and commanders to operate within distributed organizations and systems for safe and effective mission accomplishment. Tactical commanders and operators frequently encounter violent threats and critical demands on cognitive capacity and reaction time. In the future they will make decisions in situations where operational and system characteristics are highly dynamic and non-linear, i.e. minor events, decisions or actions may have serious and irreversible consequences for the entire mission. Commanders and other decision makers must manage true real time properties at all levels; individual operators, stand-alone technical systems, higher-order integrated human-machine systems and joint operations forces alike. Coping with these conditions in performance assessment, system development and operational testing is a challenge for both practitioners and researchers. This paper reports on research from which the results led to a breakthrough: An integrated approach to information-centered systems analysis to support future command and control systems research development. This approach integrates several areas of research into a coherent framework, Action Control Theory (ACT). It comprises measurement techniques and methodological advances that facilitate a more accurate and deeper understanding of the operational environment, its agents, actors and effectors, generating new and updated models. This in turn generates theoretical advances. Some good examples of successful approaches are found in the research areas of cognitive systems engineering, systems theory, and psychophysiology, and in the fields of dynamic, distributed decision making and naturalistic decision making.

Norlander, Arne↗

DOE OSTI2023

Editorial: Functional microcircuits in the brain and in artificial intelligent systems

Fundamental principles underlying higher-order cognitive functions remain elusive, but recent breakthroughs in neurophysiology and deep learning offer new perspectives. First, experimental studies have uncovered neural circuit motifs consisting of various neuron types; see Brain Initiative Cell Census Network (https://www.nature.com/collections/cicghheddj). For example, inhibitory neuron types expressing exclusive genes have specific targets and distinct functions (Pfeffer et al., 2013). Furthermore, diverse neuron types in cortex and their connectomes were identified in cortical columns (Jiang et al., 2015); see also Barth et al. (2016) for a debate on neuron types. Second, artificial neural networks were originally inspired by structures of the brain (McCulloch and Pitts, 1943) and could be trained to perform complex functions similar to human perception/cognition by deep learning (DL) (Lecun et al., 2015).

59 BASIC BIOLOGICAL SCIENCES↗