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At least 793 records · Page 44

Brain Aging Hallmarks: A Primer for Future Studies on Space Radiation Effects

As humankind endeavors to travel farther away from Earth, many questions remain to be solved to ensure proper preparation for deep space. Multiple spaceflight stressors can elicit adverse health outcomes including exposure to space radiation. Space radiation exposure has been identified by the National Aeronautics and Space Administration (NASA) as an important contributor to cancer, degenerative tissue diseases including cataracts, cardiovascular disease, immune system dysfunction and possible central nervous system decrements. The complexity of the human central nervous system makes it difficult to adequately recapitulate in experimental model systems, which hinders quantitative description of associated decrements. The brain aging hallmarks, as introduced by Mattson and Arumugam in 2018, are measurable cellular and molecular hallmarks that generally contribute to the aging process, describe an aging phenotype, and are part of the etiology of age-related neurodegenerative diseases. These hallmarks include mitochondrial dysfunction, accumulation of oxidatively damaged molecules (oxidative stress), impaired lysosome and proteasome function, dysregulation of neuronal calcium homeostasis, compromised adaptive cellular stress response, aberrant neuronal network activity, impaired deoxyribonucleic acid (DNA) repair, inflammation, impaired neurogenesis and dysregulated energy metabolism. Cellular senescence and telomere attrition may also be considered, though more evidence is needed to regard them as brain-specific hallmarks of aging. Radiation exposure has previously been correlated with aging etiology; therefore, investigating the effects of radiation exposure within the context of the hallmarks of brain aging may provide insights into potential health risks facing NASA astronauts, and may provide a means to identify disease processes that may be important targets for disease prevention or intervention. This work describes the hallmarks of brain aging and serves as a primer for future investigation into how the hallmarks of brain aging may compare and contrast with outcomes associated with exposure to the space radiation environment. Further, it will be useful in future identification of hallmarks that may be appropriate to target for radiation countermeasures specific to the central nervous system.

Vivian Lu↗

MicroRNA Based Countermeasure Rescue Health Risks Associated with Space Radiation and Microgravity

From our earlier work, we demonstrated a circulating microRNA (miRNA) signature that is present and involved with the general increased health risks during spaceflight. From this work we demonstrated that this miRNA signature impacted the overall biology and health with both the microgravity and space radiation components of the space environment. We showed that this miRNA signature can be an optimal biomarker for health risk and also has potential to be utilized as a countermeasure to mitigate the damage caused by the space environment by utilizing a human 3D microvascular tissue model. By applying a novel self-delivery system to target 3 miRNAs (i.e. antagomirs) from our spaceflight miRNA signature impacting cardiovascular health risks, we were able to completely mitigate damage caused by exposure to simulated Galactic Cosmic Ray (GCR) irradiation. Here we further expand on the countermeasure experiments to uncover the specific novel biology involved with this countermeasure and in vivo experiments that demonstrates that these antagomirs rescue damage caused to certain organs due to both microgravity and space radiation. Specifically, the miRNAs rescued damage to the heart and immune suppression that occurred in addition to other key biology. In addition, we have also observed with the 3D microvascular tissue model improved DNA double strand break repair machinery which can also contribute to improved recovery and protection against damage caused by space radiation. This work expands on our previous work and further uncovers how a potential minimally invasive countermeasure can be used to mitigate space environment effects.

Afshin Beheshti↗

ESD Reviews: Climate Feedbacks in the Earth System and Prospects for Their Evaluation

Earth system models (ESMs) are key tools for providing climate projections under different scenarios of human-induced forcing. ESMs include a large number of additional processes and feedbacks such as biogeochemical cycles that traditional physical climate models do not consider. Yet, some processes such as cloud dynamics and ecosystem functional response still have fairly high uncertainties. In this article, we present an overview of climate feedbacks for Earth system components currently included in state-of-the-art ESMs and discuss the challenges to evaluate and quantify them. Uncertainties in feedback quantification arise from the interdependencies of biogeochemical matter fluxes and physical properties, the spatial and temporal heterogeneity of processes, and the lack of long-term continuous observational data to constrain them. We present an outlook for promising approaches that can help to quantify and to constrain the large number of feedbacks in ESMs in the future. The target group for this article includes generalists with a background in natural sciences and an interest in climate change as well as experts working in interdisciplinary climate research (researchers, lecturers, and students). This study updates and significantly expands upon the last comprehensive overview of climate feedbacks in ESMs, which was produced 15 years ago (NRC, 2003).

Climate feedbacks↗

CATS-based Air Traffic Controller Agents

This report describes intelligent agents that function as air traffic controllers. Each agent controls traffic in a single sector in real time; agents controlling traffic in adjoining sectors can coordinate to manage an arrival flow across a given meter fix. The purpose of this research is threefold. First, it seeks to study the design of agents for controlling complex systems. In particular, it investigates agent planning and reactive control functionality in a dynamic environment in which a variety perceptual and decision making skills play a central role. It examines how heuristic rules can be applied to model planning and decision making skills, rather than attempting to apply optimization methods. Thus, the research attempts to develop intelligent agents that provide an approximation of human air traffic controller behavior that, while not based on an explicit cognitive model, does produce task performance consistent with the way human air traffic controllers operate. Second, this research sought to extend previous research on using the Crew Activity Tracking System (CATS) as the basis for intelligent agents. The agents use a high-level model of air traffic controller activities to structure the control task. To execute an activity in the CATS model, according to the current task context, the agents reference a 'skill library' and 'control rules' that in turn execute the pattern recognition, planning, and decision-making required to perform the activity. Applying the skills enables the agents to modify their representation of the current control situation (i.e., the 'flick' or 'picture'). The updated representation supports the next activity in a cycle of action that, taken as a whole, simulates air traffic controller behavior. A third, practical motivation for this research is to use intelligent agents to support evaluation of new air traffic control (ATC) methods to support new Air Traffic Management (ATM) concepts. Current approaches that use large, human-in-the-loop simulations are unquestionably valuable for this purpose, but pose considerable logistical, fiscal, and experimental control problems. First, data analysis is extremely complicated, owing simply to the large number of participants and data sources in such simulations. In addition, experienced human air traffic controllers working adjacent sectors tend to flexibly adapt to the evolving control problem - potentially shifting to other strategies than those under investigation. In addition, their performance is tightly coupled to the control interface, which in the development phase may support some concepts and supporting strategies better than others. A simple shift in strategy by one controller can change the character of a particular traffic scenario dramatically, which makes experimental comparison of ATC performance under different traffic scenarios difficult. Training a given team of controllers on operations under a new ATM concept for a sufficient period of time could avert such difficulties, but instituting an adequate training program is expensive and logistically difficult.

Callantine, Todd J.↗

Effect of contrast on the perceived direction of a moving plaid

A series of experiments examining the effect of contrast on the perception of moving plaids is performed. This was done to test the hypothesis put forth by Adelson and Movshon (1982) that the human visual system determines the direction of a moving plaid in a two-staged process: decomposition into component motion followed by application of the intersection of constraints rule. When the gratings within the plaid are of different contrast, the perceived direction is not predicted by the intersection of constraints rule. There is a strong (up to 20 deg) bias in the direction of the higher-contrast grating. A revised model, which incorporates a contrast-dependent weighting of perceived grating speed as observed for one-dimensional patterns (Thompson, 1982), can quantitatively predict most of the results. Results are discussed in the context of various models of human visual motion processing and of physiological responses of neurons in the primate visual system.

Stone, L. S.↗

Time series modeling of human operator dynamics in manual control tasks

A time-series technique is presented for identifying the dynamic characteristics of the human operator in manual control tasks from relatively short records of experimental data. Control of system excitation signals used in the identification is not required. The approach is a multi-channel identification technique for modeling multi-input/multi-output situations. The method presented includes statistical tests for validity, is designed for digital computation, and yields estimates for the frequency responses of the human operator. A comprehensive relative power analysis may also be performed for validated models. This method is applied to several sets of experimental data; the results are discussed and shown to compare favorably with previous research findings. New results are also presented for a multi-input task that has not been previously modeled to demonstrate the strengths of the method.

Biezad, D. J.↗

Time Series Modeling of Human Operator Dynamics in Manual Control Tasks

A time-series technique is presented for identifying the dynamic characteristics of the human operator in manual control tasks from relatively short records of experimental data. Control of system excitation signals used in the identification is not required. The approach is a multi-channel identification technique for modeling multi-input/multi-output situations. The method presented includes statistical tests for validity, is designed for digital computation, and yields estimates for the frequency response of the human operator. A comprehensive relative power analysis may also be performed for validated models. This method is applied to several sets of experimental data; the results are discussed and shown to compare favorably with previous research findings. New results are also presented for a multi-input task that was previously modeled to demonstrate the strengths of the method.

Biezad, D. J.↗

Detecting Faults By Use Of Hidden Markov Models

Frequency of false alarms reduced. Faults in complicated dynamic system (e.g., antenna-aiming system, telecommunication network, or human heart) detected automatically by method of automated, continuous monitoring. Obtains time-series data by sampling multiple sensor outputs at discrete intervals of t and processes data via algorithm determining whether system in normal or faulty state. Algorithm implements, among other things, hidden first-order temporal Markov model of states of system. Mathematical model of dynamics of system not needed. Present method is "prior" method mentioned in "Improved Hidden-Markov-Model Method of Detecting Faults" (NPO-18982).

Smyth, Padhraic J.↗

Modeling to Mars: a NASA Model Based Systems Engineering Pathfinder Effort

The NASA Engineering Safety Center (NESC) Systems Engineering (SE) Technical Discipline Team (TDT) initiated the Model Based Systems Engineering (MBSE) Pathfinder effort in FY16. The goals and objectives of the MBSE Pathfinder include developing and advancing MBSE capability across NASA, applying MBSE to real NASA issues, and capturing issues and opportunities surrounding MBSE. The Pathfinder effort consisted of four teams, with each team addressing a particular focus area. This paper focuses on Pathfinder team 1 with the focus area of architectures and mission campaigns. These efforts covered the timeframe of February 2016 through September 2016. The team was comprised of eight team members from seven NASA Centers (Glenn Research Center, Langley Research Center, Ames Research Center, Goddard Space Flight Center IV&V Facility, Johnson Space Center, Marshall Space Flight Center, and Stennis Space Center). Collectively, the team had varying levels of knowledge, skills and expertise in systems engineering and MBSE. The team applied their existing and newly acquired system modeling knowledge and expertise to develop modeling products for a campaign (Program) of crew and cargo missions (Projects) to establish a human presence on Mars utilizing In-Situ Resource Utilization (ISRU). Pathfinder team 1 developed a subset of modeling products that are required for a Program System Requirement Review (SRR)/System Design Review (SDR) and Project Mission Concept Review (MCR)/SRR as defined in NASA Procedural Requirements. Additionally, Team 1 was able to perform and demonstrate some trades and constraint analyses. At the end of these efforts, over twenty lessons learned and recommended next steps have been identified.

Phojanamongkolkij, Nipa↗

The Impact of Crop Rotation and Spatially Varying Crop Parameters in the E3SM Land Model (ELMv2)

Abstract Earth System Models (ESMs) are increasingly representing agriculture due to its impact on biogeochemical cycles, local and regional climate, and fundamental importance for human society. Realistic large scale simulations may require spatially varying crop parameters that capture crop growth at various scales and among different cultivars, as well as common crop management practices, but their importance is uncertain, and they are often not represented in ESMs. In this study, we examine the impact of using constant versus spatially varying crop parameters using a novel, realistic crop rotation scenario in the Energy Exascale Earth System Model (E3SM) Land Model version 2 (ELMv2). We implemented crop rotation by using ELMv2's dynamic land unit capability, and then calibrated and validated the model against observations collected at three AmeriFlux sites in the US Midwest with corn soybean rotation. The calibrated model closely captured the magnitude and observed seasonality of carbon and energy fluxes across crops and sites. We performed regional simulations for the US Midwest using the calibrated model and found that spatially varying only a few crop parameters across the region, as opposed to using constant parameters, had a large impact, with the carbon fluxes and energy fluxes both varying by up to 40%. These results imply that large scale ESM simulations using spatially invariant crop parameters may result in biased energy and carbon fluxes estimation from agricultural land, and underline the importance of improving human‐earth systems interactions in ESMs.

54 ENVIRONMENTAL SCIENCES↗

Automated Symbolic Upscaling: 2. Model Generation for Extended Applicability Regimes

Abstract In this second part of the two paper series, we detail an algorithmic procedure for systematically implementing the generalized closure form strategy presented in Part 1. This strategy extends the applicability of homogenized models with respect to classical homogenization theory, as demonstrated in Part 1 where upscaled models are rigorously derived in moderately reactive physical regimes. After encoding the algorithm into Symbolica, an automated upscaling framework, we upscale two reactive mass transport problems and numerically validate the resulting nonlinear homogenized models by showing the absolute error estimates predicted by homogenization theory are satisfied. In both problems, nontrivial closure forms and closure problems are automatically formulated using the encoded strategy with no human interaction, nor prior knowledge regarding the closure required for the systems. We hope these demonstrations spark further interest in automated analytical frameworks for multiscale modeling, as such capabilities are invaluable for generating rigorous multiscale models of complex phenomena in porous media.

Pietrzyk, Kyle↗

Design issues in 2-port network models of bilateral remote manipulation

A two-port impedance-network model of a single-degree-of-freedom remote manipulation system in which a human operator at the master port interacts with a task object at the slave port in a remote location is presented. The design of the network involves the selection of feedback gains for the servomechanisms that transmit motion and force information from one port of the two-port to the other in both directions. The proposed methodology allows this selection to be based on both stability requirements and specifications of desired port impedances, given models of the task and the human operator. The resulting design guidelines guarantee stability for any passive task object at the slave port and any passive human impedance at the master port.

Raju, G. Jagannath↗

National User Resource for Biological Accelerator Mass Spectrometry (Final Report)

The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide isotopic analysis (primarily radiocarbon or 14C) by accelerator mass spectrometry (AMS) for NIH- funded researchers across the United States and will be the only User Resource of its type in the United States. The User Resource will provide measurement capability and expertise to a research community that requires highly sensitive, quantitative isotope analyses. Since commissioning a new accelerator mass spectrometer in June 2014, we have measured over 4000 samples a year for collaborators and service users. The User Resource will enable us to continue to meet these research needs, as well as provide for new users whose research programs would benefit from AMS as a measurement tool. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies have been and will continue to be an important tool for addressing many complex biomedical science problems. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and other relevant radioisotopes with extreme sensitivity, having limits of detection in real samples on the order of a few attomol/mg of sample at measurement precisions of ~3%. It is the only instrumental method capable of quantifying radioisotope-labeled agents routinely in real-world samples with such precision and sensitivity. The sensitivity of AMS allows for the quantification of radiolabeled metabolites in extremely complex matrices of cells and organisms at very low concentrations and in small samples. AMS allows studies to be conducted without perturbing metabolism leading to more relevant quantification of metabolic rates and pathways. In addition, it enables quantification of pharmacokinetic and metabolic properties of toxicants at environmentally relevant concentrations in model systems as well as the ability to quantify pharmacokinetics and other molecular endpoints directly in humans. Such quantitative assessments can 1) improve risk assessment for toxicants, 2) address safety and efficacy considerations for therapeutic entities, 3) deepen understanding of xenobiotic and intermediary metabolism, 4) help understand the interactions between critical molecular pathways, and 5) improve efforts to model and predict various metabolic and biological states. These capabilities have been applied in a number of areas including research in carcinogenesis, toxicology, nutrition, pharmacology/drug development and basic biological science. As a NIGMS National Resource the National User Resource for Biological Accelerator Mass Spectrometry will help NIH funded scientists achieve a deeper understanding of the etiology of human health concerns by (1) enabling the quantification of pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids, and thereby reducing the amount of radioisotope usage in biomedical labs; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles and enable research supported by the Biophysics, Biomedical Technology, and Computational Biosciences (BBCB); Genetics and Molecular, Cellular, and Developmental Biology (GMCDB); Pharmacology, Physiology, Biological Chemistry (PPBC) and Training, Workforce Development, and Diversity (TWD) Divisions. Over the next five years, our goals are to: 1. Improve the efficiency of operation for AMS measurements through installation of new interfaces to our AMS systems, technical modifications to improve gas accepting ion source efficiency and upgrading our data analysis software for improved ease of use and data reporting. 2. Increase the accessibility and visibility of ultra-sensitive 14C measurements for the biomedical research community by training of new investigators and expanding our national user base. 3. Provide high throughput, ultra-sensitive 14C analysis for the NIGMS and NIH user community.

47 OTHER INSTRUMENTATION↗

The Applications of NASA Mission Technologies to the Greening of Human Impact

I will give an overview talk about flight software systems, robotics technologies and modeling for energy minimization as applied to vehicles and buildings infrastructures. A dominant issue in both design and operations of robotic spacecraft is the minimization of energy use. In the design and building of spacecraft increased power is acquired only at the cost of additional mass and volumes and ultimately cost. Consequently, interplanetary spacecrafts are designed to have the minimum essential power and those designs often incorporate careful timing of all power use. Operationally, the availability of power is the most influential constraint for the use of planetary surface robots, such as the Mars Exploration Rovers. The amount of driving done, the amount of science accomplished and indeed the survivability of the spacecraft itself is determined by the power available for use. For the Mars Exploration Rovers there are four tools which are used: (1) models of the rover and it s thermal and power use (2) predictive environmental models of power input and thermal environment (3) fine grained manipulation of power use (4) optimization modeling and planning tools. In this talk I will discuss possible applications of this methodology to minimizing power use on Earth, especially in buildings.

Sims, Michael H.↗

Using SCOR as a Supply Chain Management Framework for Government Agency Contract Requirements

This paper will present a model that uses the Supply-Chain Operations Reference (SCOR) model as a foundation for a framework to illustrate the information needed throughout a product lifecycle to support a healthy supply chain management function and the subsequent contract requirements to enable it. It will also show where in the supply chain the information must be extracted. The ongoing case study used to exemplify the model is NASA's (National Aeronautics and Space Administration) Ares I program for human spaceflight. Effective supply chain management and contract requirements are ongoing opportunities for continuous improvement within government agencies, specifically development of systems for human spaceflight operations. Multiple reports from the Government Accountability Office (GAO) reinforce this importance. The SCOR model is a framework for describing a supply chain with process building blocks and business activities. It provides a set of metrics for measuring supply chain performance and best practices for continuously improving. This paper expands the application of the SCOR to also provide the framework for defining information needed from different levels of the supply chain and at different phases of the lifecycle. These needs can be incorporated into contracts to enable more effective supply chain management. Depending on the phase of the lifecycle, effective supply chain management will require involvement from different levels of the organization and different levels of the supply chain.

Paxton, Joseph↗

Modeled Microgravity-Induced Protein Kinase C Isoform Expression in Human Lymphocytes

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited both in microgravity and modeled microgravity (MMG) as reflected in diminished DNA synthess in peripheral blood lymphocytes and their locomotion through gelled type 1 collagen. Direct activation of Protein Kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 19 and MMG-culture. Human lymphocytes were cultured and harvested at 24, 48, 72 and 96 hours and serial samples assessed for locomotion using type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta and -epsilon was assessed by RT-PCR, flow cytometry and immunoblotting. Results indicated that PKC isoforms delta and epsilon were down-regulated by more than 50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 19 controls. Events upstream of PKC such as phosphorylation of Phospholipase C(gamma) (PLC-gamma) in MMG, revealed accumulation of inactive enzyme. Depressed Ca++ -independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than, but after ligand-receptor interaction. Keywords: Signal transduction, locomotion, immunity

Sundaresan, A.↗

Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited in both microgravity and modeled microgravity (MMG) as reflected by diminished DNA synthesis in peripheral blood lymphocytes and their locomotion through gelled type I collagen. Direct activation of protein kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas the calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 1 g and MMG culture. Human lymphocytes were cultured and harvested at 24, 48, 72, and 96 h, and serial samples were assessed for locomotion by using type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta, and -epsilon was assessed by RT-PCR, flow cytometry, and immunoblotting. Results indicated that PKC isoforms delta and epsilon were downregulated by >50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 1-g controls. Events upstream of PKC, such as phosphorylation of phospholipase Cgamma in MMG, revealed accumulation of inactive enzyme. Depressed calcium-independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than PKC, but after ligand-receptor interaction.

Lymphocytes/enzymology↗