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DOE OSTI2024

Towards verifiable cancer digital twins: tissue level modeling protocol for precision medicine

Cancer exhibits substantial heterogeneity, manifesting as distinct morphological and molecular variations across tumors, which frequently undermines the efficacy of conventional oncological treatments. Developments in multiomics and sequencing technologies have paved the way for unraveling this heterogeneity. Nevertheless, the complexity of the data gathered from these methods cannot be fully interpreted through multimodal data analysis alone. Mathematical modeling plays a crucial role in delineating the underlying mechanisms to explain sources of heterogeneity using patient-specific data. Intra-tumoral diversity necessitates the development of precision oncology therapies utilizing multiphysics, multiscale mathematical models for cancer. This review discusses recent advancements in computational methodologies for precision oncology, highlighting the potential of cancer digital twins to enhance patient-specific decision-making in clinical settings. We review computational efforts in building patient-informed cellular and tissue-level models for cancer and propose a computational framework that utilizes agent-based modeling as an effective conduit to integrate cancer systems models that encode signaling at the cellular scale with digital twin models that predict tissue-level response in a tumor microenvironment customized to patient information. Furthermore, we discuss machine learning approaches to building surrogates for these complex mathematical models. These surrogates can potentially be used to conduct sensitivity analysis, verification, validation, and uncertainty quantification, which is especially important for tumor studies due to their dynamic nature.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1972

Panel flutter

Criteria are presented for the prediction of panel flutter, determination of its occurrence, design for its prevention, and evaluation of its severity. Theoretical analyses recommended for the prediction of flutter stability boundaries, vibration amplitudes, and frequencies for several types of panels are described. Vibration tests and wind tunnel tests are recommended for certain panels and environmental flow conditions to provide information for design of verification analysis. Appropriate design margins on flutter stability boundaries are given and general criteria are presented for evaluating the severity of possible short-duration, limited-amplitude panel flutter on nonreusable vehicles.

Dowell, E. H.↗

NASA NTRS1983

Integrated verification and testing system (IVTS) for HAL/S programs

The IVTS is a large software system designed to support user-controlled verification analysis and testing activities for programs written in the HAL/S language. The system is composed of a user interface and user command language, analysis tools and an organized data base of host system files. The analysis tools are of four major types: (1) static analysis, (2) symbolic execution, (3) dynamic analysis (testing), and (4) documentation enhancement. The IVTS requires a split HAL/S compiler, divided at the natural separation point between the parser/lexical analyzer phase and the target machine code generator phase. The IVTS uses the internal program form (HALMAT) between these two phases as primary input for the analysis tools. The dynamic analysis component requires some way to 'execute' the object HAL/S program. The execution medium may be an interpretive simulation or an actual host or target machine.

Senn, E. H.↗

NASA NTRS1985

Problems experienced and envisioned for dynamical physical systems

The use of high performance systems, which is the trend of future space systems, naturally leads to lower margins and a higher sensitivity to parameter variations and, therefore, more problems of dynamical physical systems. To circumvent dynamic problems of these systems, appropriate design, verification analysis, and tests must be planned and conducted. The basic design goal is to define the problem before it occurs. The primary approach for meeting this goal is a good understanding and reviewing of the problems experienced in the past in terms of the system under design. This paper reviews many of the dynamic problems experienced in space systems design and operation, categorizes them as to causes, and envisions future program implications, developing recommendations for analysis and test approaches.

Ryan, R. S.↗

NASA NTRS1991

Status of DSMT research program

The status of the Dynamic Scale Model Technology (DSMT) research program is presented. DSMT is developing scale model technology for large space structures as part of the Control Structure Interaction (CSI) program at NASA Langley Research Center (LaRC). Under DSMT a hybrid-scale structural dynamics model of Space Station Freedom was developed. Space Station Freedom was selected as the focus structure for DSMT since the station represents the first opportunity to obtain flight data on a complex, three-dimensional space structure. Included is an overview of DSMT including the development of the space station scale model and the resulting hardware. Scaling technology was developed for this model to achieve a ground test article which existing test facilities can accommodate while employing realistically scaled hardware. The model was designed and fabricated by the Lockheed Missile and Space Co., and is assembled at LaRc for dynamic testing. Also, results from ground tests and analyses of the various model components are presented along with plans for future subassembly and matted model tests. Finally, utilization of the scale model for enhancing analysis verification of the full-scale space station is also considered.

Mcgowan, Paul E.↗

NASA NTRS1991

Preliminary thermal design of the COLD-SAT spacecraft

The COLD-SAT free-flying spacecraft was to perform experiments with LH2 in the cryogenic fluid management technologies of storage, supply and transfer in reduced gravity. The Phase A preliminary design of the Thermal Control Subsystem (TCS) for the spacecraft exterior and interior surfaces and components of the bus subsystems is described. The TCS was composed of passive elements which were augmented with heaters. Trade studies to minimize the parasitic heat leakage into the cryogen storage tanks are described. Selection procedure for the thermally optimum on-orbit spacecraft attitude was defined. TRASYS-2 and SINDA'85 verification analysis was performed on the design and the results are presented.

Arif, Hugh↗

NASA NTRS1991

Preliminary thermal design of the COLD-SAT spacecraft

Arif, Hugh↗

NASA NTRS1993

Development of a system for transition characterization

The present system for real-time boundary layer transition detection and characterization encompasses aerodynamic simulations, sensor characteristics, and a hybrid analog/digital system for signal analysis, verification, and compression. By using artificial, intermittently laminar/turbulent signals, in conjunction with trajectory simulation, it becomes possible to conduct algorithm development which is independent of, and in advance of, sensor buildup. Attention is given to the illustrative case of the Pegasus launch vehicle's trajectory.

Bertelrud, Arild↗

NASA NTRS2000

Failure Engineering Study and Accelerated Stress Test Results for the Mars Global Surveyor Spacecraft's Power Shunt Assemblies

An Engineering-of-Failure approach to designing and executing an accelerated product qualification test was performed to support a risk assessment of a "work-around" necessitated by an on-orbit failure of another piece of hardware on the Mars Global Surveyor spacecraft. The proposed work-around involved exceeding the previous qualification experience both in terms of extreme cold exposure level and in terms of demonstrated low cycle fatigue life for the power shunt assemblies. An analysis was performed to identify potential failure sites, modes and associated failure mechanisms consistent with the new use conditions. A test was then designed and executed which accelerated the failure mechanisms identified by analysis. Verification of the resulting failure mechanism concluded the effort.

Gibbel, Mark↗

NASA NTRS2006

Toward a Framework for Modeling Space Systems Architectures

In this paper we will describe this extended RASDS/RAMSS methodology, the set of viewpoints that we have derived, and describe their relationship to RM-ODP. While this methodology may be directly used in a variety of document driven ways to describe space system architecture, the real power of it will come when there are tools available that will support full description of system architectures that can be captured electronically in a way that permits their analysis, verification, and transformation.

cost savings↗

NASA NTRS2003

International Space Station Microgravity Analytical Model Correlation And Update

The acceleration environment aboard the completed International Space Station (ISS) is a key resource for scientific and technological endeavors. Hardware verification activIties and early measurements indicate that the ISS is well on the way of meeting these "Assembly Complete" "microgravity" provisions, however, the simulation models that compute these accelerations have, to date, lacked the high degree of empirical validation typical of standard aerospace industry practices. Assembly stage, on-orbit measurements are used to address this shortcoming and to develop higher confidence in the simulation models. The Phase I correlation results show the analyses to be consistently conservative, producing higher than measured levels. The 25 to 30% greater quasi-steady computations are deemed acceptable for verification. Updates are made to localized structural dynamic and vibroacoustic parameters that reduce responses in selected one-third octave bands by almost 50%. These models are then used for the Assembly Complete verification analysis which concludes that the ISS vehicle meets the ISS microgravity requirements with minor reservations. Two of the sixteen rack are marginally non-compliant in the quasi-steady regime, and operational constraints are needed on the U. S. Lab and ESA APM vacuum resource vents, and the Russian Resistive Exercise Device in the structural dynamic regime.

DelBasso, Steve↗

NASA NTRS2014

Prediction Interval Development for Wind-Tunnel Balance Check-Loading

Results from the Facility Analysis Verification and Operational Reliability project revealed a critical gap in capability in ground-based aeronautics research applications. Without a standardized process for check-loading the wind-tunnel balance or the model system, the quality of the aerodynamic force data collected varied significantly between facilities. A prediction interval is required in order to confirm a check-loading. The prediction interval provides an expected upper and lower bound on balance load prediction at a given confidence level. A method has been developed which accounts for sources of variability due to calibration and check-load application. The prediction interval method of calculation and a case study demonstrating its use is provided. Validation of the methods is demonstrated for the case study based on the probability of capture of confirmation points.

Landman, Drew↗

NASA NTRS2018

Using Maxwell's Demon to Tame the "Devil in the Details" that are Encountered During System Development

Model-Based Systems Engineering (MBSE) is the formalized application of modeling to support system requirements, design, analysis, verification and validation activities beginning in the conceptual design phase and continuing throughout development and later life cycle phases . This presentation will discuss the value proposition that MBSE has for Systems Engineering, and the associated culture change needed to adopt it.

Model Based Systems Engineering↗

NASA NTRS2018

A Benchmark Example for Delamination Propagation Predictions Based on the Single Leg Bending Specimen Under Quasi-Static and Fatigue Loading

Benchmark examples based on Single Leg Bending (SLB) specimens with equal and unequal bending arm thicknesses were used to assess the performance of delamination prediction capabilities in finite element codes. First, the development of the quasi-static benchmark cases using the Virtual Crack Closure Technique (VCCT) is discussed in detail. Second, based on the quasi-static benchmark results, additional benchmark cases to assess delamination propagation under fatigue loading are created. Third, the application is demonstrated for the commercial finite element code Abaqus Standard 2018. The benchmark cases are compared to results obtained from VCCT-based, automated quasi-static propagation analysis. A comparison with results from automated fatigue propagation analysis was not performed at this point since the current version of Abaqus does not include this capability under variable mixed-mode conditions. In general, good agreement between the results obtained from the quasi-static propagation analysis and the benchmark results were achieved. Overall, the benchmarking procedure proved valuable for analysis verification.

Krueger, Ronald↗

NASA NTRS2020

Robustness and Behavior of Adjoint Calculations of Observation Impacts in Numerical Weather Prediction

Adjoint models are powerful tools that can be used to estimate the impact of observations on a chosen norm for numerical weather prediction forecasts. In this study, the Global Modeling and Assimilation Office (NASA/GMAO) Observing System Simulation Experiment framework is employed to investigate the behavior of the adjoint tool in an environment where the 'true' state of the atmosphere is fully known. This allows for the calculation of adjoint estimates of observation impact for very short forecast times including the zero-hour analysis state. The adjoint calculations using self-analysis verification can also be compared to adjoint calculations using the 'truth' as verification in order to characterize the robustness of adjoint estimations in the operational setting. Results from a experiments exploring various aspects of performance of the adjoint tool will be presented.

Prive, Nikki C.↗

NASA NTRSDate not supplied

A Benchmark Example for Delamination Propagation Predictions Based on the Single Leg Bending Specimen under Quasi-static and Fatigue Loading

Ronald Krueger↗

NASA NTRS2020

Observing System Simulation Experiments Investigating Atmospheric Motion Vectors and Radiances from a Constellation of 4-5 μm Infrared Sounders

A set of Observing System Simulation Experiments (OSSEs) was performed to investigate the utility of a constellation of passive infrared spectrometers, strategically designed with the aim of deriving the three-dimensional retrievals of the horizontal wind via atmospheric motion vectors (AMVs) from instruments with the spectral resolution of an infrared sounder. The instrument and constellation designs were performed in the context of the Midwave Infrared Sounding of Temperature and humidity in a Constellation for Winds, or MISTiC Winds. The Global Modeling and Assimilation Office OSSE system, which includes a full suite of operational meteorological observations, served as the control. To illustrate the potential impact of this observing strategy, two experiments were performed by adding the new simulated observations to the control. First, perfect (error-free) simulated AMVs and radiances were assimilated. Second, the data were made imperfect by adding realistic modeled errors to the AMVs and radiances that were assimilated. The experimentation showed beneficial impacts on both the mass and wind fields, as based on analysis verification, forecast verification, and the assessment of the observations using the Forecast Sensitivity to Observation Impact (FSOI) metric. In all variables and metrics, the impacts of the imperfect observations were smaller than those of the perfect observations, though much of the positive benefit was retained. The FSOI metric illustrated two key points. First, the largest impacts were seen in the middle troposphere AMVs, which is a targeted capability of the constellation strategy. Second, the addition of modeled errors showed that the assimilation system was unable to fully exploit the 4.3 μm carbon dioxide absorption radiances.

Will McCarty↗

NASA NTRS2021

Observing System Simulation Experiments Investigating Atmospheric Motion Vectors and Radiances from a Constellation of 4–5-μm Infrared Sounders

A set of observing system simulation experiments (OSSEs) was performed to investigate the utility of a constellation of passive infrared spectrometers, strategically designed with the aim of deriving the three-dimensional retrievals of the horizontal wind via atmospheric motion vectors (AMVs) from instruments with the spectral resolution of an infrared sounder. The instrument and constellation designs were performed in the context of the Midwave Infrared Sounding of Temperature and humidity in a Constellation for Winds (MISTiC Winds). The Global Modeling and Assimilation Office OSSE system, which includes a full suite of operational meteorological observations, served as the control. To illustrate the potential impact of this observing strategy, two experiments were performed by adding the new simulated observations to the control. First, perfect (error free) simulated AMVs and radiances were assimilated. Second, the data were made imperfect by adding realistic modeled errors to the AMVs and radiances that were assimilated. The experimentation showed beneficial impacts on both the mass and wind fields, as based on analysis verification, forecast verification, and the assessment of the observations using the forecast sensitivity to observation impact (FSOI) metric. In all variables and metrics, the impacts of the imperfect observations were smaller than those of the perfect observations, although much of the positive benefit was retained. The FSOI metric illustrated two key points. First, the largest impacts were seen in the middle troposphere AMVs, which is a targeted capability of the constellation strategy. Second, the addition of modeled errors showed that the assimilation system was unable to fully exploit the 4.3-μm carbon dioxide absorption radiances.

Will McCarty↗