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At least 55 records · Page 3

The Right Stuff: A Look Back at Three Decades of Flight Controller Training for Space Shuttle Mission Operations

This paper will summarize the thirty-year history of Space Shuttle operations from the perspective of training in NASA Johnson Space Center's Mission Control Center. It will focus on training and development of flight controllers and instructors, and how training practices have evolved over the years as flight experience was gained, new technologies developed, and programmatic needs changed. Operations of human spaceflight systems is extremely complex, therefore the training and certification of operations personnel is a critical piece of ensuring mission success. Mission Control Center (MCC-H), at the Lyndon B. Johnson Space Center, in Houston, Texas manages mission operations for the Space Shuttle Program, including the training and certification of the astronauts and flight control teams. This paper will give an overview of a flight control team s makeup and responsibilities during a flight, and details on how those teams are trained and certified. The training methodology for developing flight controllers has evolved significantly over the last thirty years, while the core goals and competencies have remained the same. In addition, the facilities and tools used in the control center have evolved. These changes have been driven by many factors including lessons learned, technology, shuttle accidents, shifts in risk posture, and generational differences. Flight controllers will share their experiences in training and operating the Space Shuttle throughout the Program s history. A primary method used for training Space Shuttle flight control teams is by running mission simulations of the orbit, ascent, and entry phases, to truly "train like you fly." The audience will learn what it is like to perform a simulation as a shuttle flight controller. Finally, we will reflect on the lessons learned in training for the shuttle program, and how those could be applied to future human spaceflight endeavors.

Dittemore, Gary D.↗

Identifying Outside Influences as Latent Factors to Risk in Human Performance

During the Acquisition Life Cycle for a program, there are several opportunities for the system in design to be adjusted in accordance with its changing landscape as it is being shaped by evolving policy and organizational culture. Human Systems Integration is integral to identifying these opportunities of change as there are a set number of activities that may account for altered operational states, human performance deviations, and overall component engagement if HSI is enacted early enough in the life cycle. Some changes that occur in the operational environment may not be accounted for since the organizational culture and practices are not currently a part of the HSI focus. Likewise, policy changes themselves from a top-to-bottom analysis may not have the appearance of effecting human performance until having gone through a trail-and-error period. Workarounds to adjust for unforeseen policy affects become the system's solution that usually includes changes in the training and education of the operators, maintainers, and support personnel. A system full of workarounds and off-normal practices, that cause operators to disregard the purpose of the design, coupled with the false notion that these activities are proven for successful system operation, is the very definition of “an accident waiting to happen”. Unforeseen changes in policies and practices that cause new and unusual activities to successfully and keep the system running, should be considered latent factors that may cause a potential mishap, and not part of the resilience that humans provide to the successful operation of the system. This presentation will explore how latent factors may find their way into system operations and how they can be identified and addressed.

Human Systems Integration↗

A comprehensive mission to planet Earth: Woods Hole Space Science and Applications Advisory Committee Planning Workshop

The NASA program Mission to Planet Earth (MTPE) is described in this set of visuals presented in Massachusetts on July 29, 1991. The problem presented in this document is that the earth system is changing and that human activity accelerates the rate of change resulting in increased greenhouse gases, decreasing levels of stratospheric ozone, acid rain, deforestation, decreasing biodiversity, and overpopulation. Various national and international organizations are coordinating global change research. The complementary space observations for this activity are sun-synchronous polar orbits, low-inclination, low altitude orbits, geostationary orbits, and ground measurements. The Geostationary Earth Observatory is the major proposed mission of MTPE. Other proposed missions are EOS Synthetic Aperture Radar, ARISTOTELES Magnetic Field Experiment, and the Global Topography Mission. Use of the NASA DC-8 aircraft is outlined as carrying out the Airborne Science and Applications Program. Approved Earth Probes Program include the Total Ozone Mapping Spectrometer (TOMS). Other packages for earth observation are described.

Source record↗

Brace For Impact – It’s Coming, Do You Know What to Do With It?

Long-duration human exploration spaceflight missions to the Moon and Mars present unprecedented challenges for providing in-mission medical care. Compared with the International Space Station, the greater distance from Earth will mean increased mission durations, communication delays, limited to no resupply opportunities, and significant limitations on the evacuation of ill or injured crew. Spacecraft mass, volume, and power will be curtailed while higher demands will be placed on the crew’s knowledge, skills, and abilities. In this higher risk environment, it is important to define and quantitatively estimate human system risk attributable to medical conditions. IMPACT (Informing Mission Planning via Analysis of Complex Tradespaces) is a probabilistic risk assessment (PRA) and medical trade space analysis tool being developed by NASA to advance medical system design for exploration missions. IMPACT has made a number of enhancements on the Integrated Medical Model, the PRA tool currently used by NASA. These updates include a novel medical evidence base baselined to a long duration, deep space exploration environment; an expanded medical condition list; and a trade space analysis capability (e.g. comparing risk profiles and mass/volume constraints for medical capabilities and resources). IMPACT core functionality includes quantification of a medical capability set and assisting with identification of specific medical resources/hardware for exploration missions. In addition, IMPACT provides sophisticated trade space capabilities to estimate how human system risk varies with changes to the mission architecture or medical capability set. This presentation will provide a brief overview of the IMPACT tool, discuss representative use cases, and show example results.

Benjamin Easter↗

IMPACT-ing Exploration Spaceflight Risk Prediction and Medical System Design

Human exploration spaceflight missions to the Moon and Mars present unprecedented challenges for in-mission medical care. Compared with the ISS, the greater distance from Earth will mean increased mission durations, communication delays, limited to no resupply opportunities, and significant limitations on the evacuation of ill or injured crew. Spacecraft mass, volume, and power will be curtailed while higher demands will be placed on the crew’s knowledge, skills, and abilities. In this higher risk environment, it is important to: a) quantitatively estimate human system risk attributable to medical conditions, a process known as Probabilistic Risk Analysis, and b) use these estimates to inform medical system design. IMPACT (Informing Mission Planning via Analysis of Complex Tradespaces) is a PRA and medical trade space analysis tool developed by NASA to advance exploration mission medical system design. IMPACT improves upon and will soon replace NASA’s existing tool, the Integrated Medical Model, with: a novel evidence base baselined to exploration environments; an expanded list of 120 medical conditions; a significant increase in the number of medical resources that can be utilized and in the flexibility of their use; and the modelling of time lost performing mission-specific tasks due to medical conditions. IMPACT provides evidence-based, mission-specific PRA estimates of in-flight medical risk and an initial list of clinical capabilities and medical resources/hardware to be considered. In addition, sophisticated trade space capabilities estimate how human system risk varies with changes to the mission architecture or medical capability set (e.g., if the system mass constraint decreases by 10% or ultrasound is removed). This panel will provide an overview of IMPACT, its intended use cases, and future development plans. The panel will be the first public presentation of IMPACT results, including medical risk estimates for extended duration Artemis missions, the medical conditions most influencing medical risk metrics, and the clinical capabilities that have the largest effect on medical risk.

Ben Easter↗

Assessment of the State of Communication Delay Research in Preparation for Missions Beyond Low Earth Orbit

NASA’s mission-operations paradigm, established during Project Mercury and minimally evolving through the Apollo Program, Space Shuttle Program, and ISS missions, has primarily depended on real-time support from a ground team of experts. This ground team has served as the safety net for crewed spaceflight missions over the past 60 years, managing the combined state of the mission, vehicle, and crew. However, this operational paradigm, which has seen little change in its Human-Systems Integration Architecture (HSIA), will face challenges during long-duration exploration missions beyond low Earth orbit. Lunar missions may experience one-way communication latencies ranging from 3 to 14 seconds, while Mars missions will encounter up to a 44-minute round-trip latency at a maximum distance from Earth. Communication delays negatively impact the behavioral health and performance of individuals and crews operating across the multi-team space-to-ground system. Previous research indicates that increased isolation and the challenges posed by delayed communication lead to heightened stress, frustration, adverse behavioral symptoms, and reduced individual performance. NASA has investigated the nature and effectiveness of managing this shift in complex operations since early 2000, but additional research is necessary to assess the issues associated with communication latencies and identify effective countermeasures. This work aimed to examine the evidence from 20 years of research on comm delays. We systematically reviewed the past 20 years of communication delay literature, focusing on how this research aligns with relevant, high-priority needs in the HSIA, Team, and BMed Risks. This type of panoramic review has not been done since 2013; a current, aggregated picture of what has been studied and how is needed to inform additional studies and mitigation development. Additional perspectives were gained from interviews with the research participants, operations experts, and communication delay researchers. Results from this effort will help characterize the risk posed by communication latency for upcoming Artemis missions and point toward potential mitigations. The final results will be presented. For the literature review, we formed a search term seed set drawing from languages used in two papers representative of the previous state of knowledge and supplemented it with additional search terms. We conducted literature searches on Google Scholar, PubMed, and Web of Science and searched NASA project archives for output from NASA-sponsored research. This search yielded 150 papers, of which 48 were relevant. SME interviews provided perspective on key communication delay issues and concerns and what is being worked on to mitigate those issues. Preliminary results of the literature review have been presented. Final results to be presented include the results of the literature review and findings from the interviews.

literature review↗

Linked Open Data in the Global Change Information System (GCIS)

The U.S. Global Change Research Program (http://globalchange.gov) coordinates and integrates federal research on changes in the global environment and their implications for society. The USGCRP is developing a Global Change Information System (GCIS) that will centralize access to data and information related to global change across the U.S. federal government. The first implementation will focus on the 2013 National Climate Assessment (NCA) . (http://assessment.globalchange.gov) The NCA integrates, evaluates, and interprets the findings of the USGCRP; analyzes the effects of global change on the natural environment, agriculture, energy production and use, land and water resources, transportation, human health and welfare, human social systems, and biological diversity; and analyzes current trends in global change, both human-induced and natural, and projects major trends for the subsequent 25 to 100 years. The NCA has received over 500 distinct technical inputs to the process, many of which are reports distilling and synthesizing even more information, coming from thousands of individuals around the federal, state and local governments, academic institutions and non-governmental organizations. The GCIS will present a web-based version of the NCA including annotations linking the findings and content of the NCA with the scientific research, datasets, models, observations, etc. that led to its conclusions. It will use semantic tagging and a linked data approach, assigning globally unique, persistent, resolvable identifiers to all of the related entities and capturing and presenting the relationships between them, both internally and referencing out to other linked data sources and back to agency data centers. The developing W3C PROV Data Model and ontology will be used to capture the provenance trail and present it in both human readable web pages and machine readable formats such as RDF and SPARQL. This will improve visibility into the assessment process, increase understanding and reproducibility, and ultimately increase credibility and trust of the resulting report. Building on the foundation of the NCA, longer term plans for the GCIS include extending these capabilities throughout the U.S. Global Change Research Program, centralizing access to global change data and information across the thirteen agencies that comprise the program.

Tilmes, Curt A.↗

Role of Forest Carbon Change in Shaping Future Land Use and Land Cover Change

Global change, particularly the changes in atmospheric CO 2 concentration, climatic variables, and nitrogen deposition, has been widely recognized and examined to have worldwide impacts on forest carbon. However, its influence on forest area required to meet the demand for timber and carbon storage and subsequent land use and land cover change (LULCC) is rarely studied. This study explores the role of global change-driven forest carbon change in shaping future global LULCC projections and investigates underlying drivers. We incorporated the global change impacts on forest carbon from the Canadian Land Surface Scheme Including Biogeochemical Cycles model simulations (driven by meteorological forcing projections from two Earth system models [ESMs]) into the Global Change Analysis Model, under three combinations of shared socioeconomic pathways and representative concentration pathways (SSP126, SSP370, and SSP585). Including forest carbon change decreases the projected expansion of managed forest and managed pasture, reduces the loss of unmanaged pastures and forests, and provides more cropland. The relative change in managed forest by 2100 is -4.0%, -21.7%, and -31.9%, under SSP126, SSP370, and SSP585, respectively, when forest carbon change is considered. CO 2 fertilization is the dominant driver, increasing forest vegetation and soil carbon by 37% and 4.1%, and leading to 78.6% of the total area with a change in land use types by 2100 under SSP585. In comparison, climate change reduces forest vegetation and soil carbon by -3.5% and -0.8%, influencing 23.9% of the total area with a change in land use types by 2100 under SSP585, while nitrogen deposition has minor impacts. Using meteorological forcing data from two ESMs leads to similar impacts of forest carbon change on LULCC in terms of sign and trend but different magnitudes. This study highlights the large impact of forest carbon change on shaping future LULCC dynamics and the critical role of CO 2 fertilization.

54 ENVIRONMENTAL SCIENCES↗

Effects of simulated weightlessness on regional blood flow specifically during cardiovascular stress

Significant changes in the cardiovasular system of humans and animals have been observed following exposure to prolonged periods of weightlessness during space flight. Although adaption to weightlessness is relatively uncomplicated, marked changes in cardiovascular deconditioning become evident upon return to normal gravity, including orthostatic hypotension and tachycardia. Some evidence that myocardial degeneration occurs has been demonstrated in animals who have been immobilized for two months. Also, evidence of possible loss of myocardial mass following manned space flight has been obtained by means of echocardiographic studies. These findings have serious implications in light of the increasing frequency and duration of Space Shuttle missions and the prospect of extended space station missions in the future. A number of both military and civilian investigators, including middle-aged scientists, will probably encounter prolonged periods of weightlessness. It has been imperative, therefore, to determine the effects of prolonged weightlessness on cardiovascular deconditioning and whether such effects are cumulative or reversible. The research project conducted under NASA Cooperative Agreement NCC 2-126 was undertaken to determine the effects of prolonged simulated weightlessness on regional blood flow. Research results are reported in the three appended publications.

Harrison, D. C.↗

Integrating the Interconnections Between Groundwater and Land Surface Processes Through the Coupled NASA Land Information System and ParFlow Environment

Understanding the interactions between the atmosphere, the land, and the subsurface is fundamental to hydrology and is critical for a better assessment of the impacts of climate change and human management on hydrological systems. However, many land surface models simplify the subsurface hydrology and thereby these interactions. In this study, we couple the land surface model Noah-MP included in the NASA Land Information System (LIS) with the integrated hydrologic model ParFlow (ParFlow-LIS) using the Earth System Modeling Framework (ESMF) and the National United Operational Prediction Capability (NUOPC). This coupling improves the simulation of water and energy cycle processes by adding the three-dimensional variably saturated and heterogeneous flow in the subsurface using sophisticated and nonlinear physics-based equations as well as the advances in satellite remote sensing-based data assimilation of the land surface, thereby benefiting the integrated hydrologic modeling and data assimilation community. We use the High Plains aquifer, located in the central United States, as a testbed to evaluate the coupled ParFlow-LIS system. The new ParFlow-LIS system accounts for the effects of topographically driven flows on the land surface, producing more fine-scale patterns of land surface states and fluxes than standalone LIS. In addition, ParFlow-LIS enables the consideration of the effect of subsurface water storage on evapotranspiration. This is particularly important in areas and times with dry soils, such as during drought conditions or in the presence of a cone of depression due to pumping.

land surface modeling↗

Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction

ABSTRACT Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a “top 10” list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

Microbiology↗

Sensing Super-position: Visual Instrument Sensor Replacement

The coming decade of fast, cheap and miniaturized electronics and sensory devices opens new pathways for the development of sophisticated equipment to overcome limitations of the human senses. This project addresses the technical feasibility of augmenting human vision through Sensing Super-position using a Visual Instrument Sensory Organ Replacement (VISOR). The current implementation of the VISOR device translates visual and other passive or active sensory instruments into sounds, which become relevant when the visual resolution is insufficient for very difficult and particular sensing tasks. A successful Sensing Super-position meets many human and pilot vehicle system requirements. The system can be further developed into cheap, portable, and low power taking into account the limited capabilities of the human user as well as the typical characteristics of his dynamic environment. The system operates in real time, giving the desired information for the particular augmented sensing tasks. The Sensing Super-position device increases the image resolution perception and is obtained via an auditory representation as well as the visual representation. Auditory mapping is performed to distribute an image in time. The three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. This paper details the approach of developing Sensing Super-position systems as a way to augment the human vision system by exploiting the capabilities of the human hearing system as an additional neural input. The human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns. The known capabilities of the human hearing system to learn and understand complicated auditory patterns provided the basic motivation for developing an image-to-sound mapping system.

Maluf, David A.↗

Sensing Super-Position: Human Sensing Beyond the Visual Spectrum

The coming decade of fast, cheap and miniaturized electronics and sensory devices opens new pathways for the development of sophisticated equipment to overcome limitations of the human senses. This paper addresses the technical feasibility of augmenting human vision through Sensing Super-position by mixing natural Human sensing. The current implementation of the device translates visual and other passive or active sensory instruments into sounds, which become relevant when the visual resolution is insufficient for very difficult and particular sensing tasks. A successful Sensing Super-position meets many human and pilot vehicle system requirements. The system can be further developed into cheap, portable, and low power taking into account the limited capabilities of the human user as well as the typical characteristics of his dynamic environment. The system operates in real time, giving the desired information for the particular augmented sensing tasks. The Sensing Super-position device increases the image resolution perception and is obtained via an auditory representation as well as the visual representation. Auditory mapping is performed to distribute an image in time. The three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. This paper details the approach of developing Sensing Super-position systems as a way to augment the human vision system by exploiting the capabilities of Lie human hearing system as an additional neural input. The human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns. The known capabilities of the human hearing system to learn and understand complicated auditory patterns provided the basic motivation for developing an image-to-sound mapping system. The human brain is superior to most existing computer systems in rapidly extracting relevant information from blurred, noisy, and redundant images. From a theoretical viewpoint, this means that the available bandwidth is not exploited in an optimal way. While image-processing techniques can manipulate, condense and focus the information (e.g., Fourier Transforms), keeping the mapping as direct and simple as possible might also reduce the risk of accidentally filtering out important clues. After all, especially a perfect non-redundant sound representation is prone to loss of relevant information in the non-perfect human hearing system. Also, a complicated non-redundant image-to-sound mapping may well be far more difficult to learn and comprehend than a straightforward mapping, while the mapping system would increase in complexity and cost. This work will demonstrate some basic information processing for optimal information capture for headmounted systems.

Maluf, David A.↗

Towards Designing Graceful Degradation into Trajectory Based Operations: A Human-Systems Integration Approach

One of the most fundamental changes to the air traffic management system in NextGen is the concept of trajectory based operations (TBO). With the introduction of such change, system safety and resilience is a critical concern, in particular, the ability of systems to gracefully degrade. In order to design graceful degradation into a TBO envrionment, knowledge of the potential causes of degradation, and appropriate solutions, is required. In addition, previous research has predominantly explored the technological contribution to graceful degradation, frequently neglecting to consider the role of the human operator, specifically, air traffic controllers (ATCOs). This is out of step with real-world operations, and potentially limits an ecologically valid understanding of achieving graceful degradation in an air traffic control (ATC) environment. The following literature review aims to identify and summarize the literature to date on the potential causes of degradation in ATC and the solutions that may be applied within a TBO context, with a specific focus on the contribution of the air traffic controller. A framework of graceful degradation, developed from the literature, is presented. It is argued that in order to achieve graceful degradation within TBO, a human-system integration approach must be applied.

human-system integration↗

Graph-Based Modeling for the Detection and Tracking of Sarin-Surrogate-Induced Neurotoxicity Using a Human-Relevant, In-Vitro Brain Model

Organophosphorus (OP) nerve agents are a chemical threat to the United States, to the civilian population (e.g., pesticides) and historically weaponized (e.g., sarin) as chemical warfare agents. The unprecedented, accelerated process from “bench-to-bedside” during the SARSCov2 pandemic has made it clear that technology and tools need to be readily available for immediate response. Advances in human organ tissue mimetic systems are a promising technology to evaluate the human-relevant response in vitro for basic and applied research and drug screening. In particular, current brain microphysiological systems (MPS) have the capability to monitor and detect changes in engineered human neural circuit activity. However, current data analytics approaches for these systems lack the granularity to functionally detect and distinguish the different mechanisms that occur in the brain following neurotoxicity, injury, and disease. The goal of this project was to advance the computational analytical capabilities of the brain MPS to detect functional changes in neural circuit structure at different stages of Sarin surrogate-induced neurotoxicity. We developed graph-based models to (1) identify the composition of the neural circuit structure; (2) detect and monitor how this structure changes following sarin-induced neurotoxicity; and (3) evaluate the analytical pipeline using known/promising oxime reactivators. Through experiments on the bMPS where in vitro neuronal cultures were exposed to a sarin surrogate, we demonstrated the capabilities of our computational pipeline to identify different responses in the functional networks of brain cells exposed to low and high concentrations of the nerve agent. We identified a biphasic response of human neural network activity following exposure to a sarin-surrogate that had not been reported in the literature before. The graph-based models and software developed in this project can be used for future studies that leverage the brain MPS technology, such as treatment efficacy assessment.

59 BASIC BIOLOGICAL SCIENCES↗

Strategies for Quantifying Human Space Flight Performance in the Crew Health and Performance System

The Crew Health and Performance-Probabilistic Risk Assessment (CHP-PRA) team at NASA Glenn Research Center is planning a customized approach to quantify human spaceflight performance changes with respect to changes to the CHP system functions and capabilities. Using the Directed Acyclic Graphs (DAG) initiated by NASA’s Human Systems Risk Board (HSRB) [1], the team is surveying potential candidate models and novel strategies that generate metrics suitable for supporting decision making related to how the CHP system may influence human system performance risk. One such investigation includes classic Human Reliability Analysis (HRA) models. Traditionally, HRA methods estimate the occurrence of human errors and their impact on the success of an activity when designing and operating a system. While humans perceive, interpret, decide on, and carry out a course of action, the factors affecting performance and error likelihood are commonly referred to as performance shaping factors (PSFs). Originally developed to alleviate safety concerns related to nuclear power plant operations, HRA methods such as THERP [2] and CREAM [3] dismantle an activity into tasks, requiring elemental steps to be executed, and assess their failure due to predefined PSFs. In this study, we compare generic HRA methods and those that incorporate some human spaceflight aspects, such as sleep conditions (SCREAM [4]), with respect to how they may be adopted to capture performance with an intention to mitigate detrimental outcomes elucidated by the HSRB DAGs. We suggest strategies to quantify astronaut performance specific to spaceflight activities and illustrate how such concepts may help in optimizing the CHP system capabilities with respect to Artemis missions.

dag↗

Investigation of man's immune system (M112), part B

Fifty-six days of residence in a Skylab-type environment produce essentially no change in the reactivity of the human immune system, as typified by the rate of RNA or DNA synthesis in small lymphocytes. The one point of divergence between the Skylab simulation crew and previous Apollo crews, a marked depression in synthesis rates on the fourteenth day after the chamber study, may be due to some technical difficulty in the experiment. Lymphocyte morphology changes paralleled functional changes.

Ritzmann, S. E.↗

Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent

Organophosphorus nerve agents (OPNA) are hazardous environmental exposures to the civilian population and have been historically weaponized as chemical warfare agents (CWA). OPNA exposure can lead to several neurological, sensory, and motor symptoms that can manifest into chronic neurological illnesses later in life. There is still a large need for technological advancement to better understand changes in brain function following OPNA exposure. The human-relevant in vitro multi-electrode array (MEA) system, which combines the MEA technology with human stem cell technology, has the potential to monitor the acute, sub-chronic, and chronic consequences of OPNA exposure on brain activity. However, the application of this system to assess OPNA hazards and risks to human brain function remains to be investigated. In a concentration-response study, we have employed a human-relevant MEA system to monitor and detect changes in the electrical activity of engineered neural networks to increasing concentrations of the sarin surrogate 4-nitrophenyl isopropyl methylphosphonate (NIMP). We report a biphasic response in the spiking (but not bursting) activity of neurons exposed to low (i.e., 0.4 and 4 μM) versus high concentrations (i.e., 40 and 100 μM) of NIMP, which was monitored during the exposure period and up to 6 days post-exposure. Regardless of the NIMP concentration, at a network level, communication or coordination of neuronal activity decreased as early as 60 min and persisted at 24 h of NIMP exposure. Once NIMP was removed, coordinated activity was no different than control (0 μM of NIMP). Interestingly, only in the high concentration of NIMP did coordination of activity at a network level begin to decrease again at 2 days post-exposure and persisted on day 6 post-exposure. Notably, cell viability was not affected during or after NIMP exposure. Also, while the catalytic activity of AChE decreased during NIMP exposure, its activity recovered once NIMP was removed. Gene expression analysis suggests that human iPSC-derived neurons and primary human astrocytes resulted in altered genes related to the cell’s interaction with the extracellular environment, its intracellular calcium signaling pathways, and inflammation, which could have contributed to how neurons communicated at a network level.

59 BASIC BIOLOGICAL SCIENCES↗