ALBERT

Description: Typical assays used to discover and analyze small molecules that inhibit the hepatitis C virus (HCV) NS3 helicase yield few hits and are often confounded by compound interference. Oligonucleotide binding assays are examined here as an alternative. After comparing fluorescence polarization (FP), homogeneous time-resolved fluorescence (HTRF®; Cisbio) and AlphaScreen® (Perkin Elmer) assays, an FP-based assay was chosen to screen Sigma’s Library of Pharmacologically Active Compounds (LOPAC) for compounds that inhibit NS3-DNA complex formation. Four LOPAC compounds inhibited the FP-based assay: aurintricarboxylic acid (ATA) (IC 50 = 1.4 μM), suramin sodium salt (IC 50 = 3.6 μM), NF 023 hydrate (IC 50 = 6.2 μM) and tyrphostin AG 538 (IC 50 = 3.6 μM). All but AG 538 inhibited helicase-catalyzed strand separation, and all but NF 023 inhibited replication of subgenomic HCV replicons. A counterscreen using Escherichia coli single-stranded DNA binding protein (SSB) revealed that none of the new HCV helicase inhibitors were specific for NS3h. However, when the SSB-based assay was used to analyze derivatives of another non-specific helicase inhibitor, the main component of the dye primuline, it revealed that some primuline derivatives (e.g. PubChem CID50930730) are up to 30-fold more specific for HCV NS3h than similarly potent HCV helicase inhibitors.

Description: The Advanced Resistive Exercise Device (ARED) offers crewmembers a wide range of resistance exercises but does not provide any type of load monitoring; any load data received are based on crew self-report of dialed in load. This lack of real-time ARED load monitoring severely limits research analysis. To address this issue, portable load monitoring technologies are being evaluated to act as a surrogate to ARED's failed instrumentation. The XSENS ForceShoe"TM" is a commercial portable load monitoring tool, and performed well in ground tests. The ForceShoe "TM" was recently deployed on the International Space Station (ISS), and is being evaluated as a tool to monitor ARED loads.

Description: The suite of exercise hardware aboard the International Space Station (ISS) generates an immense amount of data. The data collected, treadmill, cycle ergometer, and resistance strength training hardware, are basic exercise parameters (time, heart rate, speed, load, etc.). The raw data are processed in the laboratory and more detailed parameters are calculated from each exercise data file. Updates recently have been made to how these valuable data are stored, adding an additional level of security, increasing accessibility, and resulting in overall increased efficiency of medical report delivery. Questions regarding exercise performance or how exercise may influence other variables of crew health frequently arise within the crew health care community. Inquiries regarding the health of the exercise hardware often need quick analysis and response to ensure the exercise system is operable on a continuous basis. Consolidating all of the exercise system data in a single repository enables a quick response to both the medical and engineering communities. A SQL server database is currently in use, and provides a secure location for all of the exercise data starting at ISS Expedition 1 to current date. The database has been structured to update derived metrics automatically, making analysis and reporting available within minutes of dropping the in-flight data into the database. Commercial tools were evaluated to help aggregate and visualize data from the SQL database. The Tableau software provides manageable interface, which has improved the laboratorys output time of crew reports by 67%. Expansion of the SQL database, to be inclusive of additional medical requirement metrics, addition of app-like tools for mobile visualization, and collaborative use (e.g., operational support teams, research groups, and International Partners) of the data system, is currently being explored.

Description: During 16 years in low-Earth orbit, the suite of exercise hardware aboard the International Space Station (ISS) has matured significantly. Today, the countermeasure system supports an array of physical-training protocols and serves as an extensive research platform. Future hardware designs are required to have smaller operational envelopes and must also mitigate known physiologic issues observed in long-duration spaceflight. Taking lessons learned from the long history of space exercise will be important to successful development and implementation of future, compact exercise hardware. The evolution of exercise hardware as deployed on the ISS has implications for future exercise hardware and operations. Key lessons learned from the early days of ISS have helped to: 1. Enhance hardware performance (increased speed and loads). 2. Mature software interfaces. 3. Compare inflight exercise workloads to pre-, in-, and post-flight musculoskeletal and aerobic conditions. 4. Improve exercise comfort. 5. Develop complimentary hardware for research and operations. Current ISS exercise hardware includes both custom and commercial-off-the-shelf (COTS) hardware. Benefits and challenges to this approach have prepared engineering teams to take a hybrid approach when designing and implementing future exercise hardware. Significant effort has gone into consideration of hardware instrumentation and wearable devices that provide important data to monitor crew health and performance.

Description: Each exercise device on the International Space Station (ISS) has a unique, customized software system interface with unique layouts / hierarchy, and operational principles that require significant crew training. Furthermore, the software programs are not adaptable and provide no real-time feedback or motivation to enhance the exercise experience and/or prevent injuries. Additionally, the graphical user interfaces (GUI) of these systems present information through multiple layers resulting in difficulty navigating to the desired screens and functions. These limitations of current exercise device GUI's lead to increased crew time spent on initiating, loading, performing exercises, logging data and exiting the system. To address these limitations a Next Generation One Portal (NextGen One Portal) Crew Countermeasure System (CMS) was developed, which utilizes the latest industry guidelines in GUI designs to provide an intuitive ease of use approach (i.e., 80% of the functionality gained within 5-10 minutes of initial use without/limited formal training required). This is accomplished by providing a consistent interface using common software to reduce crew training, increase efficiency & user satisfaction while also reducing development & maintenance costs. Results from the usability evaluations showed the NextGen One Portal UI having greater efficiency, learnability, memorability, usability and overall user experience than the current Advanced Resistive Exercise Device (ARED) UI used by astronauts on ISS. Specifically, the design of the One-Portal UI as an app interface similar to those found on the Apple and Google's App Store, assisted many of the participants in grasping the concepts of the interface with minimum training. Although the NextGen One-Portal UI was shown to be an overall better interface, observations by the test facilitators noted specific exercise tasks appeared to have a significant impact on the NextGen One-Portal UI efficiency. Future updates to the NextGen One Portal UI will address these inefficiencies.

Description: The suite of exercise hardware aboard the International Space Station (ISS) generates an immense amount of data. The data collected from the treadmill, cycle ergometer, and resistance strength training hardware are basic exercise parameters (time, heart rate, speed, load, etc.). The raw data are post processed in the laboratory and more detailed parameters are calculated from each exercise data file. Updates have recently been made to how this valuable data are stored, adding an additional level of data security, increasing data accessibility, and resulting in overall increased efficiency of medical report delivery. Questions regarding exercise performance or how exercise may influence other variables of crew health frequently arise within the crew health care community. Inquiries over the health of the exercise hardware often need quick analysis and response to ensure the exercise system is operable on a continuous basis. Consolidating all of the exercise system data in a single repository enables a quick response to both the medical and engineering communities. A SQL server database is currently in use, and provides a secure location for all of the exercise data starting at ISS Expedition 1 - current day. The database has been structured to update derived metrics automatically, making analysis and reporting available within minutes of dropping the inflight data it into the database. Commercial tools were evaluated to help aggregate and visualize data from the SQL database. The Tableau software provides manageable interface, which has improved the laboratory's output time of crew reports by 67%. Expansion of the SQL database to be inclusive of additional medical requirement metrics, addition of 'app-like' tools for mobile visualization, and collaborative use (e.g. operational support teams, research groups, and International Partners) of the data system is currently being explored.

Description: Heart rate monitoring is required for crewmembers during exercise aboard the International Space Station (ISS) and will be for future exploration missions. The cardiovascular system must be sufficiently stressed throughout a mission to maintain the ability to perform nominal and contingency/emergency tasks. High quality heart rate data are required to accurately determine the intensity of exercise performed by the crewmembers and show maintenance of VO2max. The quality of the data collected on ISS is subject to multiple limitations and is insufficient to meet current requirements. PURPOSE: To evaluate the performance of commercially available Bluetooth heart rate monitors (BT_HRM) and their ability to provide high quality heart rate data to monitor crew health aboard the ISS and during future exploration missions. METHODS: Nineteen subjects completed 30 data collection sessions of various intensities on the treadmill and/or cycle. Subjects wore several BT_HRM technologies for each testing session. One electrode-based chest strap (CS) was worn, while one or more optical sensors (OS) were worn. Subjects were instrumented with a 12-lead ECG to compare the heart rate data from the Bluetooth sensors. Each BT_HRM data set was time matched to the ECG data and a +/-5bpm threshold was applied to the difference between the 2 data sets. Percent error was calculated based on the number of data points outside the threshold and the total number of data points. RESULTS: The electrode-based chest straps performed better than the optical sensors. The best performing CS was CS1 (1.6% error), followed by CS4 (3.3% error), CS3 (6.4% error), and CS2 (9.2% error). The OS resulted in 10.4% error for OS1 and 14.9% error for OS2. CONCLUSIONS: The highest quality data came from CS1, but unfortunately it has been discontinued by the manufacturer. The optical sensors have not been ruled out for use, but more investigation is needed to determine how to obtain the best quality data. CS2 will be used in an ISS Bluetooth validation study, because it simultaneously transmits magnetic pulse that is integrated with existing exercise hardware on ISS. The simultaneous data streams allow for beat-to-beat comparison between the current ISS standard and CS2. Upon Bluetooth validation aboard ISS, the research team will down select a new BT_HRM for operational use.

Description: Astronauts perform exercise throughout their missions to counter the health declines that occur as a result of long-term exposure to weightlessness. Although all astronauts perform exercise during their missions, the specific prescriptions, and thus the mechanical loading, differs among individuals. For example, inflight ground reaction force data indicate that subject-specific differences exist in foot forces created when exercising on the second-generation treadmill (T2) [1]. The current exercise devices allow astronauts to complete prescriptions at higher intensities, resulting in greater benefits with increased efficiency. Although physiological outcomes have improved, the specific factors related to the increased benefits are unknown. In-flight exercise hardware collect data that allows for exploratory analyses to determine if specific performance factors relate to physiological outcomes. These analyses are vital for understanding which components of exercise are most critical for optimal human health and performance. The relationship between exercise performance variables and physiological changes during flight has yet to be fully investigated. Identifying the critical performance variables that relate to improved physiological outcomes is vital for creating current and future exercise prescriptions to optimize astronaut health. The specific aims of this project are: 1) To quantify the exercise-related mechanical loading experienced by crewmembers on T2 and ARED during their mission on ISS; 2) To explore relationships between exercise loading variables, bone, and muscle health changes during the mission; 3) To determine if specific mechanical loading variables are more critical than others in protecting physiology; 4) To develop methodology for operational use in monitoring accumulated training loads during crew exercise programs. This retrospective analysis, which is currently in progress, is being conducted using data from astronauts that have flown long-duration missions onboard the ISS and have had access to exercise on the T2 and the Advanced Resistive Exercise Device (ARED). The specific exercise prescriptions vary for each astronaut. General exercise summary metrics will be developed to quantify exercise intensities, volumes, and durations for each subject. Where available, ground reaction force data will be used to quantify mechanical loading experienced by each astronaut. These inflight exercise metrics will be investigated relative to changes in pre- to post-flight bone and muscle health to identify which specific variables are related with improved or degraded physiological outcomes. The information generated from this analysis will fill gaps related to typical bone loading characterization, exercise performance capability, exercise volume and efficiency, and importance of exercise hardware. In addition, methods for quantification of exercise loading for use in monitoring the exercise programs during future space missions will be explored with the intent to inform exercise scientists and trainers as to the critical aspects of inflight exercise prescriptions.