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At least 55 records · Page 3

Cancer genomics predicts disease relapse and therapeutic response to neoadjuvant chemotherapy of hormone sensitive breast cancers

Several studies provide insight into the landscape of breast cancer genomics with the genomic characterization of tumors offering exceptional opportunities in defining therapies tailored to the patient’s specific need. However, translating genomic data into personalized treatment regimens has been hampered partly due to uncertainties in deviating from guideline based clinical protocols. Here we report a genomic approach to predict favorable outcome to treatment responses thus enabling personalized medicine in the selection of specific treatment regimens. The genomic data were divided into a training set of N = 835 cases and a validation set consisting of 1315 hormone sensitive, 634 triple negative breast cancer (TNBC) and 1365 breast cancer patients with information on neoadjuvant chemotherapy responses. Patients were selected by the following criteria: estrogen receptor (ER) status, lymph node invasion, recurrence free survival. The k-means classification algorithm delineated clusters with low- and high- expression of genes related to recurrence of disease; a multivariate Cox’s proportional hazard model defined recurrence risk for disease. Classifier genes were validated by Immunohistochemistry (IHC) using tissue microarray sections containing both normal and cancerous tissues and by evaluating findings deposited in the human protein atlas repository. Based on the leave-on-out cross validation procedure of 4 independent data sets we identified 51-genes associated with disease relapse and selected 10, i.e. TOP2A, AURKA, CKS2, CCNB2, CDK1 SLC19A1, E2F8, E2F1, PRC1, KIF11 for in depth validation. Expression of the mechanistically linked disease regulated genes significantly correlated with recurrence free survival among ER-positive and triple negative breast cancer patients and was independent of age, tumor size, histological grade and node status. Importantly, the classifier genes predicted pathological complete responses to neoadjuvant chemotherapy (P < 0.001) with high expression of these genes being associated with an improved therapeutic response toward two different anthracycline-taxane regimens; thus, highlighting the prospective for precision medicine. Our study demonstrates the potential of classifier genes to predict risk for disease relapse and treatment response to chemotherapies. The classifier genes enable rational selection of patients who benefit best from a given chemotherapy thus providing the best possible care. The findings encourage independent clinical validation.

59 BASIC BIOLOGICAL SCIENCES↗

Proposed Reliability-Based Damage Tolerance Guidelines for Space Systems

Deterministic damage tolerance guidelines for highly reusable and efficiently designed launch systems can be challenging to meet and result in overly conservative assessments for tightly controlled manufacturing processes. Deterministic approaches may be unconservative when the structure is workmanship sensitive and there is a wide spread in fracture properties. Reliability-based damage tolerance assessments targeting a component reliability over the service life commensurate to mission risk posture is a promising alternative. Low production rates, short fleets, and lack of standards or guidance has slowed down widespread adoption of this method. Guidance for the robust application of reliability-based damage tolerance for space systems are proposed. These guidelines cover the treatment of uncertainty in damage tolerance analysis, the collection of data to develop probabilistic distributions, uncertainty propagation methods, and types of hardware.

Reliability-Based Damage Tolerance↗

Proposed Modifications to Engineering Design Guidelines Related to Resistivity Measurements and Spacecraft Charging

A key parameter in modeling differential spacecraft charging is the resistivity of insulating materials. This determines how charge will accumulate and redistribute across the spacecraft, as well as the time scale for charge transport and dissipation. Existing spacecraft charging guidelines recommend use of tests and imported resistivity data from handbooks that are based principally upon ASTM methods that are more applicable to classical ground conditions and designed for problems associated with power loss through the dielectric, than for how long charge can be stored on an insulator. These data have been found to underestimate charging effects by one to four orders of magnitude for spacecraft charging applications. A review is presented of methods to measure the resistive of highly insulating materials, including the electrometer-resistance method, the electrometer-constant voltage method, the voltage rate-of-change method and the charge storage method. This is based on joint experimental studies conducted at NASA Jet Propulsion Laboratory and Utah State University to investigate the charge storage method and its relation to spacecraft charging. The different methods are found to be appropriate for different resistivity ranges and for different charging circumstances. A simple physics-based model of these methods allows separation of the polarization current and dark current components from long duration measurements of resistivity over day- to month-long time scales. Model parameters are directly related to the magnitude of charge transfer and storage and the rate of charge transport. The model largely explains the observed differences in resistivity found using the different methods and provides a framework for recommendations for the appropriate test method for spacecraft materials with different resistivities and applications. The proposed changes to the existing engineering guidelines are intended to provide design engineers more appropriate methods for consideration and measurements of resistivity for many typical spacecraft charging scenarios.

Dennison, J. R.↗

Field Test: Results of Tandem Walk Performance Following Long-Duration Spaceflight

BACKGROUND: Coordinated locomotion has proven to be challenging for many astronauts following long duration spaceflight. As NASA's vision for spaceflight points toward interplanetary travel, we must prepare for unassisted landings, where crewmembers may need to perform mission critical tasks within minutes of landing. Thus, it is vital to develop a knowledge base from which operational guidelines can be written that define when astronauts can be expected to safely perform certain tasks. Data obtained during the Field Test experiment (FT) will add important insight to this knowledge base. Specifically, we aim to develop a recovery timeline of functional sensorimotor performance during the first 24 hours and several days after landing. METHODS: FT is an ongoing study of 30 long-duration ISS crewmembers. Thus far, 9 have completed the full FT (5 U.S. Orbital Segment [USOS] astronauts and 4 Russian cosmonauts) and 4 more consented and launching within the next year. This is in addition to the eighteen crewmembers that participated in the pilot FT (11 USOS and 7 Russian crewmembers). The FT is conducted three times preflight and three times during the first 24 hours after landing. All crewmembers were tested in Kazakhstan in either the medical tent at the Soyuz landing site (~one hour post-landing), or at the airport (~four hours post-landing). The USOS crewmembers were also tested at the refueling stop (~12 hours post-landing) and at the NASA Johnson Space Center (~24 hours post-landing) and a final session 7 days post-landing. Crewmembers are instrumented with 9 inertial measurement unit sensors that measure acceleration and angular displacement (APDM's Emerald Sensors) and foot pressure-sensing insoles that measure force, acceleration, and center of pressure (Moticon GmbH, Munich, Germany) along with heart rate and blood pressure recording instrumentation. The FT consists of 12 tasks, but here we will focus on the most challenging task, the Tandem Walk, which was also performed as part of pilot FT. To perform the Tandem Walk, subjects begin with their feet together, their arms crossed at their chest and eyes closed. When ready, they brought one foot forward and touched the heel of their foot to their toe, repeating with the other foot, and continuing for about 10 steps. Three trials were collected with the eyes closed and a fourth trial was collected with eyes open. There are four metrics which are used to determine the performance level of the Tandem Walk. The first is percent correct steps. For a step to be counted as correct, the foot could not touch the ground while bringing it forward (no side stepping), eyes must stay closed during the eyes closed trials, the heel and toe should be touching, or almost touching (no large gaps) and there shouldn't be more than a three second pause between steps. Three judges score each step and the median of the three scores is kept. The second metric is the average step speed, or the number of steps/time to complete them. Thirdly, the root mean squared (RMS) error in the resultant trunk acceleration is used to determine the amount of upper body instability observed during the task. Finally, the RMS error of the mediolateral center of pressure as measured by the Moticon insoles is used to determine the mediolateral instability at the foot level. These four parameters are combined into a new overall Tandem Walk Parameter. RESULTS: Preliminary results show that crewmembers perform the Tandem Walk significantly worse the first 24 hours after landing as compared to their baseline performance. We find that each of the four performance metrics is significantly worse immediately after landing. We will present the results of tandem walk performance during the FT thus far. We will also combine these with the 18 crewmembers that participated in the pilot FT, concentrating on the level of performance and recovery rate. CONCLUSION: The Tandem Walk data collected as part of the FT experiment will provide invaluable information on the performance capabilities of astronauts during the first 24 hours after returning from long-duration spaceflight that can be used in planning future Mars, or other deep-space missions with unassisted landings. FT will determine the average sensorimotor recovery timeline and inform return-to-duty guidelines for unassisted landings.

Rosenberg, M. J. F.↗

Pilot Field Test: Results of Tandem Walk Performance Following Long-Duration Spaceflight

Coordinated locomotion has proven to be challenging for many astronauts following long duration spaceflight. As NASA's vision for spaceflight points toward interplanetary travel and missions to distant objects, astronauts will not have assistance once they land. Thus, it is vital to develop a knowledge base from which operational guidelines can be written that define when astronauts can be expected to safely perform certain tasks. Data obtained during the Field Test experiment will add important insight to this knowledge base. Specifically, we aim to develop a recovery timeline of functional sensorimotor performance during the first 24 hours and several days after landing. A forerunner of the full Field Test study, the Pilot Field Test (PFT) comprised a subset of the tasks and measurements to be included in the ultimate set.

Cerisano, J. M.↗

Developing a Prototype Methodology to Rank CO2-EOR Wells and Assess Their Reuse Potential for Geologic Carbon Sequestration

This study presents a prototype methodology for evaluating the reuse potential of Class II CO₂-enhanced oil recovery (CO₂-EOR) wells as Class VI wells for geologic carbon sequestration. The approach focuses on assessing wellbore construction materials—casing, cement, tubing, and packers—based on U.S. Environmental Protection Agency (EPA) Class VI well conversion guidelines. Utilizing Python scripts and JSON representations, the methodology automates checks on digitized Texas Railroad Commission (TRRC) data to rank wells based on regulatory and integrity criteria. Key factors include casing integrity, cementing techniques, tubing compatibility, and packer selection. Due to limitations in digitized data, manual verification is required for certain sections. Future enhancements include incorporating non-digitized data via web scraping and machine learning. This research provides a practical framework for well owners and regulators, supporting informed decision-making for sustainable CO₂ storage.

carbon sequestration↗

Line Pilots' Attitudes about and Experience with Flight Deck Automation: Results of an International Survey and Proposed Guidelines

A survey of line pilots' attitudes about flight deck automation was conducted by the Royal Air Force Institute of Aviation Medicine (RAF IAM, Farnborough, UK) under the sponsorship of the United Kingdom s Civil Aviation Authority and in cooperation with IATA (the International Air Transport Association). Survey freehand comments given by pilots operating 13 types of commercial transports across five manufacturers (Airbus, Boeing, British Aerospace, Lockheed, and McDonnell-Douglas) and 57 air carriers/organizations were analyzed by NASA. These data provide a "lessons learned" knowledge base which may be used for the definition of guidelines for flight deck automation and its associated crew interface within the High Speed Research Program. The aircraft chosen for analysis represented a progression of levels of automation sophistication and complexity, from "Basic" types (e.g., B727, DC9), through "Transition" types (e.g., A300, Concorde), to two levels of glass cockpits (e.g., Glass 1: e.g., A310; Glass 2: e.g., B747-400). This paper reports the results of analyses of comments from pilots flying commercial transport types having the highest level of automation sophistication (B757/B767, B747-400, and A320). Comments were decomposed into five categories relating to: (1) general observations with regard to flight deck automation; comments concerning the (2) design and (3) crew understanding of automation and the crew interface; (4) crew operations with automation; and (5) personal factors affecting crew/automation interaction. The goal of these analyses is to contribute to the definition of guidelines which may be used during design of future aircraft flight decks.

Rudisill, Marianne↗

Efficient and assured reinforcement learning-based building HVAC control with heterogeneous expert-guided training

Abstract Building heating, ventilation, and air conditioning (HVAC) systems account for nearly half of building energy consumption and $$20\%$$ of total energy consumption in the US. Their operation is also crucial for ensuring the physical and mental health of building occupants. Compared with traditional model-based HVAC control methods, the recent model-free deep reinforcement learning (DRL) based methods have shown good performance while do not require the development of detailed and costly physical models. However, these model-free DRL approaches often suffer from long training time to reach a good performance, which is a major obstacle for their practical deployment. In this work, we present a systematic approach to accelerate online reinforcement learning for HVAC control by taking full advantage of the knowledge from domain experts in various forms . Specifically, the algorithm stages include learning expert functions from existing abstract physical models and from historical data via offline reinforcement learning, integrating the expert functions with rule-based guidelines, conducting training guided by the integrated expert function and performing policy initialization from distilled expert function. Moreover, to ensure that the learned DRL-based HVAC controller can effectively keep room temperature within the comfortable range for occupants, we design a runtime shielding framework to reduce the temperature violation rate and incorporate the learned controller into it. Experimental results demonstrate up to 8.8 X speedup in DRL training from our approach over previous methods, with low temperature violation rate.

Xu, Shichao↗

Selected results for LDEF thermal control coatings

The investigation of space environmental effects on LDEF thermal control coatings by the Materials Special Investigation Group is continuing. Analyses of chromic acid anodize, A276 white paint, and Z306 black paint were conducted, assessing performance as functions of environmental exposure. Test results from additional coatings, such as on scuff plates, M003, and the black chromium plate solar absorber, were obtained. Guidelines for the use of these materials and comparisons to ground based test data will be presented.

Golden, Johnny L.↗

Pitfalls and Precautions When Using Predicted Failure Data for Quantitative Analysis of Safety Risk for Human Rated Launch Vehicles

Launch vehicle reliability analysis is largely dependent upon using predicted failure rates from data sources such as MIL-HDBK-217F. Reliability prediction methodologies based on component data do not take into account risks attributable to manufacturing, assembly, and process controls. These sources often dominate component level reliability or risk of failure probability. While consequences of failure is often understood in assessing risk, using predicted values in a risk model to estimate the probability of occurrence will likely underestimate the risk. Managers and decision makers often use the probability of occurrence in determining whether to accept the risk or require a design modification. Due to the absence of system level test and operational data inherent in aerospace applications, the actual risk threshold for acceptance may not be appropriately characterized for decision making purposes. This paper will establish a method and approach to identify the pitfalls and precautions of accepting risk based solely upon predicted failure data. This approach will provide a set of guidelines that may be useful to arrive at a more realistic quantification of risk prior to acceptance by a program.

Hatfield, Glen S.↗

Pitfalls and Precautions When Using Predicted Failure Data for Quantitative Analysis of Safety Risk for Human Rated Launch Vehicles

Launch vehicle reliability analysis is largely dependent upon using predicted failure rates from data sources such as MIL-HDBK-217F. Reliability prediction methodologies based on component data do not take into account system integration risks such as those attributable to manufacturing and assembly. These sources often dominate component level risk. While consequence of failure is often understood, using predicted values in a risk model to estimate the probability of occurrence may underestimate the actual risk. Managers and decision makers use the probability of occurrence to influence the determination whether to accept the risk or require a design modification. The actual risk threshold for acceptance may not be fully understood due to the absence of system level test data or operational data. This paper will establish a method and approach to identify the pitfalls and precautions of accepting risk based solely upon predicted failure data. This approach will provide a set of guidelines that may be useful to arrive at a more realistic quantification of risk prior to acceptance by a program.

Hatfield, Glen S.↗

Update on Activities Related to the Library of Graphite Microstructures

This report provides an overview and update of the ongoing efforts to create a comprehensive library of microstructures for nuclear graphite and carbon-based materials under consideration for nuclear applications. The library includes data on microstructural characterization of unirradiated graphite materials, a guide to the techniques used to analyze graphite (which complements the ASME guidelines and ASTM standards), a summary of characterization data for neutron-irradiated or oxidized material, and a compendium of microstructural information for carbon-based materials. These efforts are being conducted at various length scales for the filler and binder phases in graphite to better understand graphite’s local structure and property relationships. This report is a follow-up to the previous milestone report titled Report on initial development of a database of nuclear graphite characteristics based on microstructural characterization, ORNL/TM/-2023/2992, published in July 2023.The effort to develop the library of microstructures supports the US Department of Energy Office of Advanced Reactor Technologies program objectives of aiding the material selection, licensing, management, and core assessments of a graphite core by documenting the unirradiated microstructure of relevant grades or characterizing the microstructure’s evolution under the reactor environment. Additionally, this project aims to provide (1) information and guidelines for the characterizing of graphite and (2) a protocol to assess a nuclear graphite grade.

36 MATERIALS SCIENCE↗

Establishing viable task domains for telerobot demonstrations

A suite of telerobotic tasks has been compiled and assessed for the purpose of selecting viable tasks for near and far term laboratory demonstrations. The primary intent of developing the task is to provide some technical guidelines, with supporting data, for focusing laboratory demonstrations toward application domains that address a wide array of potential telerobot tasks and required technologies. This wide application would then result in a rich technology development environment to meet the broad task requirements of a system such as the Flight Telerobot Servicer. The methodology and results of the telerobot task assessment are described, including a ranking of the final select suite of major tasks. The presented along with guidelines for both interpreting the task ranking results and setting programmatic objectives based on these results. Detailed data about the task candidates and their respective levels of complexity, task primitive actions, and the actual relative measures of task worth as associated with key tradeoff variables such as cost, available research resources, technology availability, and importance to the user community are also presented.

Zimmerman, Wayne↗

Spacecraft Water Exposure Guidelines for Selected Contaminants

The International Space Station is a closed and complex environment, so some contamination of its internal atmosphere and water system is expected. To protect space crews from contaminants in potable and hygiene water, the National Aeronautics and Space Administration (NASA) requested that the National Research Council (NRC) provide guidance on how to develop water exposure guidelines and review NASA s development of the exposure guidelines for specific chemicals. NASA selects water contaminants for which spacecraft water exposure guidelines (SWEGs) will be established; this involves identifying toxicity effects relevant to astronauts and calculating exposure concentrations on the basis of those end points. SWEGs are established for exposures of 1, 10, 100, and 1,000 days. This report is the second volume in the series, Spacecraft Water Exposure Guidelines for Selected Chemicals. SWEG reports for acetone, alkylamines, ammonia, barium, cadmium, caprolactam, formate, formaldehyde, manganese, total organic carbon, and zinc are included in this report. The committee concludes that the SWEGs developed for these chemicals are scientifically valid based on the data reviewed by NASA and are consistent with the NRC (2000) report, Methods for Developing Spacecraft Water Exposure Guidelines. SWEG reports for additional chemicals will be presented in a subsequent volume.

Source record↗

Earthdata User Interface (EUI) Library

As more remote sensing data moves to the cloud, the design tools we use to build user experiences and visualizations need to change and adapt to make the best use this new data reality. EUI 2.0, the next major iteration of the Earthdata User Interface Library, aims to make creating rich user experiences around NASA's Earth Observation System Data and Information System (EOSDIS) data easy and user-friendly. Building on a solid framework of design components, EUI 2.0 will be open source and have off-the-shelf integration with the Common Metadata Repository (CMR), basic mapping and visualization tools, a refreshed design toolkit for building apps and websites that fit the Earthdata design theme and guidelines. EUI 2.0 will allow for the rapid development of websites and applications based on EOSDIS tools and data holdings. It will also make use of cloud data availability to enable data visualization and analysis without the need to download and sync data.

Siarto, Jeff↗

Principles for Termination of Medical Care in Austere Analog Environments for Development of Spaceflight Protocols

INTRODUCTION: When compared to operations in low earth orbit, exploration class missions will have substantially limited resources and ground medical support while the risk of a significant medical event is projected to be higher. Termination of care (TOC) may need to be considered in certain instances. We aim to utilize data from earth-based analogs to identify common principles that can help develop future guidelines to this complex medical and ethical challenge. METHODS: A comprehensive literature review was conducted in medline, nasa.gov, Defense Technical Information Center(DTIC) and google scholar. Key search terms including “withdrawal of care, termination of care, termination of CPR, military medicine, wilderness medicine, futility, potentially inappropriate” and others were used to identify analog studies of relevance. These were qualitatively evaluated for recurring principles or themes that were reviewed and structured. RESULTS: Mission planning termination of care principles: definitions of clear medical goals, separate protocols for each relevant condition, protocols developed using best available evidence, crew involvement in development, protocols rehearsal pre-launch, and inclusion of palliative capabilities. In-mission termination of care principles: 1. Crew Medical Officer directed stabilization of the patient; 2. Consultation with mission control with standardized information exchange; 3. Multidisciplinary medical and ethical conference among the mission directors, flight surgeons and relevant specialist experts; 4. Multidisciplinary risk review examining both medical and mission risks for relevant options; 5. Provision of a transparent explanation of the process and decision to crew; 6. Allowing crew feedback and inquiry to review board; 7. Support of the crew in the enacted decision. DISCUSSION: By utilizing the best available evidence in conjunction with expert opinion we have identified common principles from earth-based analogs that could be used to help design future TOC protocols.

Samuel Stephenson↗

Design Guidelines for the Application of Forebody and Nose Strakes to a Fighter Aircraft Based on F-16 Wind Tunnel Testing Experience

During the YF-16 and F-16 developmental wind tunnel test program, numerous variations in nose and forebody strakes were investigated. These data were reviewed, and the strake aerodynamic characteristics coalesced into design guidelines for the application of strakes to fighter aircraft. The design guides take the form of general equations governing the modification of forebody strakes to obtain a linear pitching moment curve and the calculation of the resulting lift and drag increments. Additionally, qualitative comments are made concerning the effects of strake geometry on lateral/directional stability. It is concluded that the generation of incremental strake lift is primarily dependent upon the area affected by the strake-induced vortex and that strake planform is of secondary importance. Forebody strakes have small beneficial effects on lateral/directional stability if properly designed; however, significant gains are easily attained with nose strakes.

Smith, C. W.↗

Guidelines for VCCT-Based Interlaminar Fatigue and Progressive Failure Finite Element Analysis

This document is intended to detail the theoretical basis, equations, references and data that are necessary to enhance the functionality of commercially available Finite Element codes, with the objective of having functionality better suited for the aerospace industry in the area of composite structural analysis. The specific area of focus will be improvements to composite interlaminar fatigue and progressive interlaminar failure. Suggestions are biased towards codes that perform interlaminar Linear Elastic Fracture Mechanics (LEFM) using Virtual Crack Closure Technique (VCCT)-based algorithms [1,2]. All aspects of the science associated with composite interlaminar crack growth are not fully developed and the codes developed to predict this mode of failure must be programmed with sufficient flexibility to accommodate new functional relationships as the science matures.

Deobald, Lyle R.↗