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At least 307 records · Page 17

Mutually promoting or constraining? Disentangling the superimposed effect of velocity and illuminance on fish motion in low-velocity flows with a novel metric

Global climate change, species invasion, and human activities such as the construction of hydraulic facilities are contributing to the worldwide degradation of fish stocks. As a pivotal environmental factor that affects fish migration and population distribution, low-velocity flow has not drawn enough attention despite its extensive presence in various ecoregions. Herein, to understand the behavioural profiles of fish in low-velocity flow, we examined the motility and swimming performance of two representative cyprinids, grass carp (GC, Ctenopharyngodon idella) and silver carp (SC, Hypophthalmichthys molitrix), under the combined effect of different flow velocities and illuminance ranges. The two species were exposed to two flow velocities (0.15 and 0.25 m/s) and three illuminance ranges (100.0 – 0.9 lx, 300.0 – 2.5 lx, and 700.0 – 4.9 lx). A novel behavioural metric, composed of light preference, cruising swimming speed, rheotaxis index (RI), swimming stability (SS), and the probability of moving forwards/backwards over a certain distance (PM f -0.1 and PM b -0.1), was developed to depict the motion strategy of fish fully. By investigating the individual distribution of the fish in light gradient, we confirmed the scototaxis of GC and found the oscillating light preference in SC that changed from 84.4 – 10.2 lx to 6.0 – 2.1 lx and disappeared with increasing illuminance. At the given velocities, the RI and SS increased in both species with a faster flow, and SC was more forward-prone and stable than GC. Despite its fluctuating light preference, the higher illuminances heightened the RI and SS in SC; while in GC, higher illuminances inhibited the SS and had no impact on the RI. The results of PM f -0.1 and PM b -0.1 indicated that a higher flow velocity could facilitate temporary upstream swimming in both species, while illuminance could promote the same effect in SC only. Finally, our study proposed possible moving manoeuvres in fine-scale spatio-temporal scenarios such as attraction flow and untraditional passages and provides valuable insights into fish community dynamics, laying the groundwork for alleviating the threat from invasive species and for future fish population recovery.

59 BASIC BIOLOGICAL SCIENCES↗

Air Traffic Controller Acceptability of Unmanned Aircraft System Detect-and-Avoid Thresholds

A human-in-the-loop experiment was conducted with 15 retired air traffic controllers to investigate two research questions: (a) what procedures are appropriate for the use of unmanned aircraft system (UAS) detect-and-avoid systems, and (b) how long in advance of a predicted close encounter should pilots request or execute a separation maneuver. The controller participants managed a busy Oakland air route traffic control sector with mixed commercial/general aviation and manned/UAS traffic, providing separation services, miles-in-trail restrictions and issuing traffic advisories. Controllers filled out post-scenario and post-simulation questionnaires, and metrics were collected on the acceptability of procedural options and temporal thresholds. The states of aircraft were also recorded when controllers issued traffic advisories. Subjective feedback indicated a strong preference for pilots to request maneuvers to remain well clear from intruder aircraft rather than deviate from their IFR clearance. Controllers also reported that maneuvering at 120 seconds until closest point of approach (CPA) was too early; maneuvers executed with less than 90 seconds until CPA were more acceptable. The magnitudes of the requested maneuvers were frequently judged to be too large, indicating a possible discrepancy between the quantitative UAS well clear standard and the one employed subjectively by manned pilots. The ranges between pairs of aircraft and the times to CPA at which traffic advisories were issued were used to construct empirical probability distributions of those metrics. Given these distributions, we propose that UAS pilots wait until an intruder aircraft is approximately 80 seconds to CPA or 6 nmi away before requesting a maneuver, and maneuver immediately if the intruder is within 60 seconds and 4 nmi. These thresholds should make the use of UAS detect and avoid systems compatible with current airspace procedures and controller expectations.

unmanned aircraft systems↗

2021–2022 Can Do Colorado E-Bike Full-Scale Pilot Program Study

In 2021–2022, the Colorado Energy Office conducted a full-scale pilot program study on e-bike usage as part of the Can Do Colorado initiative, providing e-bikes to low-income participants across the state. A [2020 mini pilot program study](https://www.nlr.gov/transportation/secure-transportation-data/tsdc-2020-can-do-colorado-e-bike-pilot-program.html) informed the full-scale study. Both studies used pedal-assist e-bikes, which feature an electric motor and battery to help power the bike. The motor amplifies the power behind each pedal stroke, augmenting the energy you put into the bike. #### Data Collection Agency The Colorado Energy Office conducted the study in partnership with local organizations in Adams and Broomfield counties (Smart Commute Metro North), Boulder (Community Cycles), Durango (Four Corners Office for Resource Efficiency), Fort Collins (City of Fort Collins), Pueblo (Pueblo County), and Vail (Town of Vail). #### Survey Methodology Program participants received an e-bike and accessories at no cost and manually submitted travel data and feedback via the CanBikeCO smartphone app. Developed in partnership with NLR, the app used a customized version of the open-source [NLR OpenPATH platform](https://www.nlr.gov/transportation/openpath.html). #### Survey Records and Data Survey records include 170 participants. The six datasets contain up to 18 months of partially automated travel diaries, combining sensed and surveyed travel behavior data—patterns of multimodal, end-to-end, individual human mobility—as well as demographic information from participants. The number of e-bike trips and e-bike miles traveled per location are 1,560 and 4,179 for Adams and Broomfield counties; 8,481 and 27,000 for Boulder; 2,815 and 6,307 for Durango; 3,483 and 7,080 for Fort Collins; 4,022 and 14,887 for Pueblo, and 1,206 and 3,3361 for Vail.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

The Final Approach Spacing Tool

A system for assisting terminal area air traffic controllers in the management and control of arrival traffic, referred to as the Final Approach Spacing Tool (FAST), is being developed at NASA Ames Research Center. In a cooperative program, NASA and FAA have efforts underway to install and evaluate the system at the Dallas/Fort Worth Terminal Radar Approach Control facility. This paper will review the software architecture, the algorithms components, and the human-machine interface. The system is based on continuous updates of a detailed trajectory analyses of all arrival aircraft. FAST interprets the results of these trajectory analyses to build an efficient and procedurally acceptable plan for the arrival traffic that consists of a sequence, schedule, and runway assignment. The system utilizes a heuristically-based conflict resolution algorithm to build a solution trajectory that satisfies the plan, It extracts a series of speed and heading advisories from the solution trajectory to assist the controller in efficiently managing and controlling the arrival traffic down to the runway. The advisories are displayed in a graphical format to the controller. In addition to the radar tracking data, the system also relies on a series of data bases. These data bases contain aircraft performance models, airline preferred operational procedures, airspace structure, air traffic procedural models, and a three dimensional wind model. Field evaluation of FAST is expected to begin in 1994.

Davis, Thomas J.↗

Vertex Movement for Mission Status Graphics: A Polar-Star Display

Humans are traditionally bad monitors, especially over long periods of time on reliable systems, and they are being called upon to do this more and more as systems become further automated. Because of this, there is a need to find a way to display the monitoring information to the human operator in such a way that he can notice pertinent deviations in a timely manner. One possible solution is to use polar-star displays that will show deviations from normal in a more salient manner. A polar-star display uses a polygon's vertices to report values. An important question arises, though, of how the vertices should move. This experiment investigated two particular issues of how the vertices should move: (1) whether the movement of the vertices should be continuous or discrete and (2) whether the parameters that made up each vertex should always move in one direction regardless of parameter sign or move in both directions indicating parameter sign. The results indicate that relative movement direction is best. Subjects performed better with this movement type and they subjectively preferred it to the absolute movement direction. As for movement type, no strong preferences were shown.

Trujillo, Anna↗

Synaptic Zn2+ potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior

Abstract Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn 2+ ) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn 2+ concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control subjects. Moreover, the level of striatal Zn 2+ content in these subjects negatively correlated with plasma levels of benzoylecgonine, a cocaine metabolite indicative of recent use. In mice, repeated cocaine exposure increased synaptic Zn 2+ concentrations in the caudate putamen (CPu) and nucleus accumbens (NAc). Cocaine-induced increases in Zn 2+ were dependent on the Zn 2+ transporter 3 (ZnT3), a neuronal Zn 2+ transporter localized to synaptic vesicle membranes, as ZnT3 knockout (KO) mice were insensitive to cocaine-induced increases in striatal Zn 2+ . ZnT3 KO mice showed significantly lower electrically evoked DA release and greater DA clearance when exposed to cocaine compared to controls. ZnT3 KO mice also displayed significant reductions in cocaine locomotor sensitization, conditioned place preference (CPP), self-administration, and reinstatement compared to control mice and were insensitive to cocaine-induced increases in striatal DAT binding. Finally, dietary Zn 2+ deficiency in mice resulted in decreased striatal Zn 2+ content, cocaine locomotor sensitization, CPP, and striatal DAT binding. These results indicate that cocaine increases synaptic Zn 2+ release and turnover/metabolism in the striatum, and that synaptically released Zn 2+ potentiates the effects of cocaine on striatal DA neurotransmission and behavior and is required for cocaine-primed reinstatement. In sum, these findings reveal new insights into cocaine’s pharmacological mechanism of action and suggest that Zn 2+ may serve as an environmentally derived regulator of DA neurotransmission, cocaine pharmacodynamics, and vulnerability to cocaine use disorders.

60 APPLIED LIFE SCIENCES↗

ISS Propulsion Module Crew Systems Interface Analysis in the Intelligent Synthesis Environment

ERGO, a human modeling software for ergonomic assessment and task analysis, was used for the crew systems interface analysis of the International Space Station (ISS) Propulsion Module (PM). The objective of analysis was to alleviate passageway size concerns. Three basic passageway configuration concepts: (1) 45" clear passageway without centerline offset (2) 50" clear passageway, 12" centerline offset, (3) 50" clear passageway, no centerline offset, and were reviewed. 95 percentile male and female models which were provided by the software performed crew system analysis from an anthropometric point of view. Four scenarios in which the crew floats in microgravity through a 50" no-offset passageway as they carry a 16" x 20" x 30" avionics box were simulated in the 10-weeks of intensive study. From the results of the analysis, concept (3) was the preferred option. A full scale, three-dimensional virtual model of the ISS Propulsion Module was created to experience the sense of the Intelligent Synthesis Environment and to evaluate the usability and applicability of the software.

Chen, Di-Wen↗

NASA Technical Standards Program and Implications for Lessons Learned and Technical Standard Integration

The National Aeronautics and Space Agency consists of fourteen Facilities throughout the United States. They are organized to support the Agency's principal Enterprises: (1) Space Science, (2) Earth Science, (3) Aerospace Technology, (4) Human Exploration and Development of Space, and (5) Biological and Physical Research. Technical Standards are important to the activities of each Enterprise and have been an integral part in the development and operation of NASA Programs and Projects since the Agency was established in 1959. However, for years each Center was responsible for its own standards development and selection of non-NASA technical standards that met the needs of Programs and Projects for which they were responsible. There were few Agencywide applicable Technical Standards, mainly those in area of safety. Department of Defense Standards and Specifications were the foundation and main source for Technical Standards used by the Agency. This process existed until about 1997 when NASA embarked on a Program to convert NASA's Center-developed Technical Standards into Agencywide endorsed NASA Preferred Technical Standards. In addition, action was taken regarding the formal adoption of non-NASA Technical Standards (DOD, SAE, ASTM, ASME, IEEE, etc.) as NASA Preferred Technical Standards.

Gill, Paul S.↗

Multidimensional Data Aggregation in the Cloud with Application to Geostationary Satellite-based Air Quality Monitoring

Scientists use satellite data for studying Earth's systems, and the remote sensing data that these satellites collect are typically separated into files of a size small enough for efficient network transfer and storage. However, researchers usually prefer to analyze the data based on real-world dimensions like time, space, or elevation. To help with this, NASA's Atmospheric Science Data Center (ASDC) developed a new cloud-based tool that combines these smaller data chunks into larger, more useful datasets. The tool works on Network Common Data Form (netCDF4) and some HDF5 formatted files, and it is available as a service in NASA's Earthdata Cloud. In this presentation, we showcase this service using data from the Tropospheric Emissions: Monitoring of Pollution (TEMPO) instrument. By combining TEMPO's continuous observations over time, we create longer and more informative analysis-ready time series to facilitate the study of air quality patterns. Insights gained will provide a more comprehensive understanding of pollution sources, transport patterns, and their effects on the environment and human health.

Daniel Kaufman↗

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

NASA Discipline Neuroscience↗

Characterizing the effects of droplines on target acquisition performance on a 3-D perspective display

The present study investigated the effects of droplines on target acquisition performance on a 3-D perspective display in which participants were required to move a cursor into a target cube as quickly as possible. Participants' performance and coordination strategies were characterized using both Fitts' law and acquisition patterns of the 3 viewer-centered target display dimensions (azimuth, elevation, and range). Participants' movement trajectories were recorded and used to determine movement times for acquisitions of the entire target and of each of its display dimensions. The goodness of fit of the data to a modified Fitts function varied widely among participants, and the presence of droplines did not have observable impacts on the goodness of fit. However, droplines helped participants navigate via straighter paths and particularly benefited range dimension acquisition. A general preference for visually overlapping the target with the cursor prior to capturing the target was found. Potential applications of this research include the design of interactive 3-D perspective displays in which fast and accurate selection and manipulation of content residing at multiple ranges may be a challenge.

Time and Motion Studies↗

Runway Configuration Management with Offline Reinforcement Learning

Runway configuration management (RCM) is a challenging task, and it affects the efficiency of the National Airspace System (NAS) and airport surface operations significantly. Each airport, depending on the geometry, capacity, local climate patterns, etc. has multiple configurations for the runway usage for arriving and departing flights. Many factors such as the incoming/outgoing traffic load, wind direction and speed, convective weather, cloud ceiling and other environmental factors might affect the choice of a runway configuration at any point in time. However, other factors such as safety measures and regulations, noise abatement, capacity of each configuration, and preference of the air traffic controllers (ATCs) can also play a significant role in selecting the configuration. A sub-optimal selection of the runway configuration, or delay in making configuration changes might result in significant increase in taxi times for aircraft on the surface of the airport, fuel and energy use of the aircraft, and maintenance costs. It can also lead to safety concerns, such as an aircraft performing one or more go-arounds before being able to land. All these factors make RCM an extremely important and challenging decision-making process for the ATCs. The current state of practice sets the runway configuration by the ATCs based on relevant information available at the time including weather, traffic, noise abatement, safety bounds, etc. This makes the decision-making process subjective based on the accuracy of the available information and the bias in human decision making. Unfortunately, this approach yields poor results (e.g., significant delays) if the predicted outcomes are uncertain and their relative impact is not well understood. This is especially evident when the uncertainty increases the size of possible predicted outcomes (combinatorial explosion in possible scenarios) that cannot be handled by human reasoning. On the other hand, an automated approach based on machine intelligence can make use of historical data and search through all (or significant amount of) possible scenarios under uncertainty and make well-informed decisions.

Milad Memarzadeh↗

Human Factors Evaluation of Conflict Detection Tool for Terminal Area

A conflict detection and resolution tool, Terminal-area Tactical Separation-Assured Flight Environment (T-TSAFE), is being developed to improve the timeliness and accuracy of alerts and reduce the false alert rate observed with the currently deployed technology. The legacy system in use today, Conflict Alert, relies primarily on a dead reckoning algorithm, whereas T-TSAFE uses intent information to augment dead reckoning. In previous experiments, T-TSAFE was found to reduce the rate of false alerts and increase time between the alert to the controller and a loss of separation over the legacy system. In the present study, T-TSAFE was tested under two meteorological conditions, 1) all aircraft operated under instrument flight regimen, and 2) some aircraft operated under mixed operating conditions. The tool was used to visually alert controllers to predicted Losses of separation throughout the terminal airspace, and show compression errors, on final approach. The performance of T-TSAFE on final approach was compared with Automated Terminal Proximity Alert (ATPA), a tool recently deployed by the FAA. Results show that controllers did not report differences in workload or situational awareness between the T-TSAFE and ATPA cones but did prefer T-TSAFE features over ATPA functionality. T-TSAFE will provide one tool that shows alerts in the data blocks and compression errors via cones on the final approach, implementing all tactical conflict detection and alerting via one tool in TRACON airspace.

Verma, Savita Arora↗

Plant Nitrogen Uptake Responses to Elevated Carbon Dioxide

Future long-duration missions will require a sustainable supply of food to support human crews. The spaceflight cabin environment often contains very high concentrations of CO 2 due to release of CO 2 by astronauts that is not completely scrubbed from the cabin, and it is therefore crucial to understand plant responses to elevated CO 2 (eCO 2 ) environments. Much focus has been given to changes in plant photosynthetic and performance parameters in response to eCO 2 , but the effects of eCO 2 on nitrogen (N) uptake are poorly understood. Shoot nitrate reduction may be reduced at eCO 2 , likely due to less reductant available for nitrate reduction because of reduced photorespiration and increased carbon fixation 1. Relative growth rate can be reduced at eCO 2 when N is provided only as nitrate and can be unaffected when N is supplied as ammonium. However, N uptake in response to eCO 2 has, to our knowledge, not yet been studied. An increased ‘preference’ for plants to take up N as ammonium at eCO 2 could have important implications for growth in the space environment, where N is currently only supplied as nitrate. In this study, novel stable isotope approaches were used in conjunction with hydroponics and isotope ratio mass spectrometry to determine the effect of eCO 2 on N preference for ammonium or nitrate in spring barley and lettuce when both N forms are provided equally. Several varieties of spring barley displayed increased ammonium preference at eCO 2 (720 ppm) compared to ambient CO 2 (410 ppm), though this was not true for all varieties. In most cases, increases in ammonium preference were driven by increases in ammonium uptake at eCO 2 and not decreases in nitrate uptake. Current research is assessing whether similar responses are observed in the candidate space crop lettuce, at levels of CO 2 like those observed on ISS (3000 ppm), and these results will also be presented. This work will enable the development of optimized nutrient regimes for candidate crops in space environments and the selection of crop varieties adapted to eCO 2 environments. Plants adapted to ammonium nutrition may play a role in future plant-based bioregenerative life support systems with higher ammonium concentrations due to waste recycling. Moreover, this research will further our understanding of plant responses to the eCO 2 environment brought about by climate change, allowing the development of future-proof crops that will help to maintain food security.

nitrogen↗

Impact of Different Trajectory Option Set Participation Levels within an Air Traffic Management Collaborative Trajectory Option Program

This paper presents the methodology and results of a Human-In-The-Loop (HITL) simulation study conducted in the Airspace Operations Laboratory at NASA Ames Research Center. This study is a part of NASA's ongoing research into developing an Integrated Demand Management (IDM) concept, whose aim is to improve traffic flow management (TFM) by coordinating the FAA's strategic Traffic Flow Management System (TFMS) with its more tactical Time-Based Flow Management (TBFM) system. The purpose of TFM is to regulate air traffic demand so that it is delivered efficiently through constrained airspace resources without exceeding their capacity limits. The IDM concept leverages a new TFMS capability called the Collaborative Trajectory Options Program (CTOP) to strategically pre-condition traffic demand flowing into a TBFM-managed arrival environment, where TBFM is responsible for managing traffic tactically by generating precise arrival schedules. Unlike other TFM tools, CTOP gives flight operators the option of submitting a set of user-preferred alternative trajectories for each flight. CTOP can then use these trajectory option sets (or TOSs) to find user-preferred alternative routes to reduce demand on an overloaded resource. CTOP's effectiveness in redistributing demand is limited, however, by the availability of flights with alternative routes. The research presented in this paper focuses on evaluating the impact on TFM operations by varying the percentage of flights that submit a multiple-option TOS ('TOS participation levels'). Results show the impact on overall system performance and on the rerouted flights themselves. The simulation used a Newark (EWR) airport arrival scenario, with en route weather affecting traffic inbound from the west. Participants were asked to control each of the three arrival flows (north, west, and south) to meet their individual capacity constraints while simultaneously ensuring efficient utilization of the capacity at the destination airport. A large, permeable convective weather cell located southeast of Chicago severely reduced the capacity of the west flow. The study evaluated the impact of five different TOS participation levels on CTOP's ability to re-allocate traffic from the west and improve TFM performance in terms of delay assignment and traffic delivery rate to the airport. Overall, the results showed that increasing TOS submissions allowed the overall system delays to be reduced and fairly distributed among the three arrival flows, at the same time achieving the airport throughput rate. Moreover, it was found that aircraft who submitted a TOS saw a greater reduction in delay, even when they were assigned longer routes. This was particularly true when fewer aircraft submitted a TOS. The results confirm that the CTOP operations with higher TOS participation levels helped utilize the overall National Airspace System (NAS) resources as well as benefited the users who participated.

Yoo, Hyo-Sang↗

Human-In-The-Loop Investigation of Interoperability Between Terminal Sequencing and Spacing, Automated Terminal Proximity Alert, and Wake-Separation Recategorization

A human-in-the-loop simulation study addressed terminal-area controller-workstation interface variations for interoperability between three new capabilities being introduced by the FAA. The capabilities are Terminal Sequencing and Spacing (TSAS), Automated Terminal Proximity Alert (ATPA), and wake-separation recategorization, or 'RECAT.' TSAS provides controllers with Controller-Managed Spacing (CMS) tools, including slot markers, speed advisories, and early/late indications, together with runway assignments and sequence numbers. ATPA provides automatic monitor, warning, and alert cones to inform controllers about spacing between aircraft on approach. ATPA cones are sized according to RECAT, an improved method of specifying wake-separation standards. The objective of the study was to identify potential issues and provide recommendations for integrating TSAS with ATPA and RECAT. Participants controlled arrival traffic under seven different display configurations, then tested an 'exploratory' configuration developed with participant input. All the display conditions were workable and acceptable, but controllers strongly preferred having the CMS tools available on Feeder positions, and both CMS tools and ATPA available on Final positions. Controllers found the integrated systems favorable and liked being able to tailor configurations to individual preferences.

ATD-1↗

Microbial Monitoring of the International Space Station

Humans living and working in the harsh environment of space present many challenges for habitability engineers and microbiologists. Spacecraft must provide an internal environment in which physical (gas composition, pressure, temperature, and humidity), chemical, and biological environmental parameters are maintained at safe levels. Microorganisms are ubiquitous and will accompany all human-occupied spacecraft, but if biological contamination were to reach unacceptable levels, long-term human space flight would be impossible. Prevention of microbiological problems, therefore, must have a high priority. Historically, prevention of infectious disease in the crew has been the highest priority, but experience gained from the NASA-Mir program showed that microbial contamination of vehicle and life-support systems, such as biofouling of water and food, are of equal importance. The major sources of microbiological risk factors for astronauts include food, drinking water, air, surfaces, payloads, research animals, crew members, and personnel in close contact with the astronauts. In our efforts to eliminate or mitigate the negative effects of microorganisms in spacecraft, the National Aeronautics and Space Administration (NASA) implemented comprehensive microbial analyses of the major risk factors. This included the establishment of acceptability requirements for food, water, air, surfaces, and crew members. A robust monitoring program was then implemented to verify that the risks were within acceptable limits. Prevention of microbiological problems is preferred over mitigation of problems during flight, and preventive steps must begin very early in the design phase. Spacecraft development must include requirements to control free water from humidity, condensate, hygiene activities, and other releases. If water is available, microbes are likely to grow because sufficient nutrients are potentially available. Materials selected for the spacecraft must not promote or support microbial growth. Air filtration can dramatically reduce the number of airborne bacteria, fungi, and particulates in spacecraft breathing air. Waterborne bacteria can be reduced to acceptable levels by thermal inactivation of bacteria during water processing, along with a residual biocide, and filtration at the point of use can ensure safety. System design must include onboard capability to achieve recovery of the system from contamination. Robust housekeeping procedures that include periodic cleaning and disinfection will prevent high levels of microbial growth on surfaces. Food for consumption in space must be thoroughly tested for excessive microbial content and pathogens before launch. Thorough preflight examination of flight crews, consumables, payloads, and the environment can greatly reduce pathogens in spacecraft. Many of the lessons learned from the Space Shuttle and previous programs were applied in the early design phase of the International Space Station, resulting in the safest space habitat to date. This presentation describes the monitoring program for the International Space Station and will summarize results from preflight and on-orbit monitoring.

Pierson, Duane L.↗

Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, in this work we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗