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Evidence for a membrane defect in Alzheimer disease brain

To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

NASA Discipline Regulatory Physiology↗

The ALTEA/ALTEINO projects: studying functional effects of microgravity and cosmic radiation

The ALTEA project investigates the risks of functional brain damage induced by particle radiation in space. A modular facility (the ALTEA facility) is being implemented and will be operated in the International Space Station (ISS) to record electrophysiological and behavioral descriptors of brain function and to monitor their time dynamics and correlation with particles and space environment. The focus of the program will be on abnormal visual perceptions (often reported as "light flashes" by astronauts) and the impact on retinal and brain visual structures of particle in microgravity conditions. The facility will be made available to the international scientific community for human neurophysiological, electrophysiological and psychophysics experiments, studies on particle fluxes, and dosimetry. A precursor of ALTEA (the 'Alteino' project) helps set the experimental baseline for the ALTEA experiments, while providing novel information on the radiation environment onboard the ISS and on the brain electrophysiology of the astronauts during orbital flights. Alteino was flown to the ISS on the Soyuz TM34 as part of mission Marco Polo. Controlled ground experiments using mice and accelerator beams complete the experimental strategy of ALTEA. We present here the status of progress of the ALTEA project and preliminary results of the Alteino study on brain dynamics, particle fluxes and abnormal visual perceptions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

manned↗

Countermeasure for space flight effects on immune system: nutritional nucleotides

Microgravity and its environment have adverse effects on the immune system. Abnormal immune responses observed in microgravity may pose serious consequences, especially for the recent directions of NASA for long-term space missions to Moon, Mars and deep Space exploration. The study of space flight immunology is limited due to relative inaccessibility, difficulty of performing experiments in space, and inadequate provisions in this area in the United States and Russian space programs (Taylor 1993). Microgravity and stress experienced during space flights results in immune system aberration (Taylor 1993). In ground-based mouse models for some of the microgravity effects on the human body, hindlimb unloading (HU) has been reported to cause abnormal cell proliferation and cytokine production (Armstrong et al., 1993, Chapes et al. 1993). In this report, we document that a nutritional nucleotide supplementation as studied in ground-based microgravity analogs, has potential to serve as a countermeasure for the immune dysfunction observed in space travel.

NASA Center JSC↗

Modification of Eccentric Gaze-Holding

Clear vision and accurate localization of objects in the environment are prerequisites for reliable performance of motor tasks. Space flight confronts the crewmember with a stimulus rearrangement that requires adaptation to function effectively with the new requirements of altered spatial orientation and motor coordination. Adaptation and motor learning driven by the effects of cerebellar disorders may share some of the same demands that face our astronauts. One measure of spatial localization shared by the astronauts and those suffering from cerebellar disorders that is easily quantified, and for which a neurobiological substrate has been identified, is the control of the angle of gaze (the "line of sight"). The disturbances of gaze control that have been documented to occur in astronauts and cosmonauts, both in-flight and postflight, can be directly related to changes in the extrinsic gravitational environment and intrinsic proprioceptive mechanisms thus, lending themselves to description by simple non-linear statistical models. Because of the necessity of developing robust normal response populations and normative populations against which abnormal responses can be evaluated, the basic models can be formulated using normal, non-astronaut test subjects and subsequently extended using centrifugation techniques to alter the gravitational and proprioceptive environment of these subjects. Further tests and extensions of the models can be made by studying abnormalities of gaze control in patients with cerebellar disease. A series of investigations were conducted in which a total of 62 subjects were tested to: (1) Define eccentric gaze-holding parameters in a normative population, and (2) explore the effects of linear acceleration on gaze-holding parameters. For these studies gaze-holding was evaluated with the subjects seated upright (the normative values), rolled 45 degrees to both the left and right, or pitched back 30 and 90 degrees. In a separate study the further effects of acceleration on gaze stability was examined during centrifugation (+2 G (sub x) and +2 G (sub z) using a total of 23 subjects. In all of our investigations eccentric gaze-holding was established by having the subjects acquire an eccentric target (+/-30 degrees horizontal, +/- 15 degrees vertical) that was flashed for 750 msec in an otherwise dark room. Subjects were instructed to hold gaze on the remembered position of the flashed target for 20 sec. Immediately following the 20 sec period, subjects were cued to return to the remembered center position and to hold gaze there for an additional 20 sec. Following this 20 sec period the center target was briefly flashed and the subject made any corrective eye movement back to the true center position. Conventionally, the ability to hold eccentric gaze is estimated by fitting the natural log of centripetal eye drifts by linear regression and calculating the time constant (G) of these slow phases of "gaze-evoked nystagmus". However, because our normative subjects sometimes showed essentially no drift (tau (sub c) = m), statistical estimation and inference on the effect of target direction was performed on values of the decay constant theta = 1/(tau (sub c)) which we found was well modeled by a gamma distribution. Subjects showed substantial variance of their eye drifts, which were centrifugal in approximately 20 % of cases, and > 40% for down gaze. Using the ensuing estimated gamma distributions, we were able to conclude that rightward and leftward gaze holding were not significantly different, but that upward gaze holding was significantly worse than downward (p<0.05). We also concluded that vertical gaze holding was significantly worse than horizontal (p<0.05). In the case of left and right roll, we found that both had a similar improvement to horizontal gaze holding (p<0.05), but didn't have a significant effect on vertical gaze holding. For pitch tilts, both tilt angles significantly decreased gaze-holding ility in all directions (p<0.05). Finally, we found that hyper-g centrifugation significantly decreased gaze holding ability in the vertical plane. The main findings of this study are as follows: (1) vertical gaze-holding is less stable than horizontal, (2) gaze-holding to upward targets is less stable than to downward targets, (3) tilt affects gaze holding, and (4) hyper-g affects gaze holding. This difference between horizontal and vertical gaze-holding may be ascribed to separate components of the velocity-to-position neural integrator for eye movements, and to differences in orbital mechanics. The differences between upward and downward gaze-holding may be ascribed to an inherent vertical imbalance in the vestibular system. Because whole body tilt and hyper-g affects gaze-holding, it is implied that the otolith organs have direct connections to the neural integrator and further studies of astronaut gaze-holding are warranted. Our statistical method for representing the range of normal eccentric gaze stability can be readily applied to normals who maybe exposed to environments which may modify the central integrator and require monitoring, and to evaluate patients with gaze-evoked nystagmus by comparing to the above established normative criteria.

Reschke, M. F.↗

Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

Cucinotta, Francis A.↗

Aircraft Emergencies: Challenge and Response

Emergency and abnormal situations in aviation present flight crews with a number of challenges. Checklists are essential tools that have been developed to assist them to meet these challenges. However, in order for checklists to be most effective in these situations they must be designed with the operational and situational demands of emergencies and abnormal conditions in mind as well as human performance capabilities and limitations under high stress and workload.

Burian, Barbara K.↗

Comparison of Two Digital Stethoscopes with the Traditional Stethoscope Used on International Space Station

A traditional stethoscope is currently flown on the International Space Station (ISS). The background noise on the ISS is much higher than a normal exam room, and the literature shows that traditional stethoscopes are unable to function effectively in high noise environments. Digital stethoscopes provide amplification which improves the audibility in a quiet environment. This study is designed to determine if digital stethoscopes offer any advantage over traditional stethoscopes in being able to identify normal and abnormal sounds in the ISS noise environment. Methods: An ISS noise simulation facility was created to reproduce ISS noise profiles by modifying pink noise with a software-based graphic equalizer. The files were played in a continuous loop on a computer, amplified through a high-end stereo system and adjusted using a sound level meter. Nine caregiver analogues were given the same auscultation lesson received by astronauts. They began testing by becoming familiar with normal and abnormal sounds on a Student Auscultation Manikin . They then used two digital stethoscopes and a traditional stethoscope identical to the one flown on the ISS to auscultate the manikin sounds in the noise facility. They identified the sounds on a questionnaire and picked which of the three stethoscopes they preferred. Results: Evaluators displayed equivalent accuracy in sound identification when using either the 3M model 4000 digital stethoscope or traditional stethoscope. However, the 3M was preferred 2 to 1 by the evaluators, primarily because of additional amplification of the sounds. Discussion: Although our results show that the current ISS stethoscope and the "best-of-breed" digital stethoscope provide essentially the same auscultation utility, the latter has the advantage of recording and transmitting sounds to a remote physician. Since the astronaut caregivers are non-physiCians, this capability may be worth the additional expense and effort needed to certify the digital stethoscope for flight.

Rasbury, Jack↗

Multi-Sensors Observations of Pre-Earthquake Signals. What We Learned from the Great Tohoku Earthquake?

The lessons learned from the Great Tohoku EQ (Japan, 2011) will affect our future observations and an analysis is the main focus of this presentation. Multi-sensors observations and multidisciplinary research is presented in our study of the phenomena preceding major earthquakes Our approach is based on a systematic analysis of several physical and environmental parameters, which been reported by others in connections with earthquake processes: thermal infrared radiation; temperature; concentration of electrons in the ionosphere; radon/ion activities; and atmospheric temperature/humidity [Ouzounov et al, 2011]. We used the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC) model, one of several possible paradigms [Pulinets and Ouzounov, 2011] to interpret our observations. We retrospectively analyzed the temporal and spatial variations of three different physical parameters characterizing the state of the atmosphere, ionosphere the ground surface several days before the March 11, 2011 M9 Tohoku earthquake Namely: (i) Outgoing Long wave Radiation (OLR) measured at the top of the atmosphere; (ii) Anomalous variations of ionospheric parameters revealed by multi-sensors observations; and (iii) The change in the foreshock sequence (rate, space and time); Our results show that on March 8th, 2011 a rapid increase of emitted infrared radiation was observed and an anomaly developed near the epicenter with largest value occurring on March 11 at 07.30 LT. The GPS/TEC data indicate an increase and variation in electron density reaching a maximum value on March 8. Starting from this day in the lower ionosphere there was also observed an abnormal TEC variation over the epicenter. From March 3 to 11 a large increase in electron concentration was recorded at all four Japanese ground-based ionosondes, which returned to normal after the main earthquake. We use the Japanese GPS network stations and method of Radio Tomography to study the spatiotemporal structure of ionospheric perturbations, and to distinguish ionospheric responses to processes of EQ preparation against the effects of other factors. The 2-D snapshots of the electron density over Japan showed abnormal increase over the maximum stress during the night, a few hours before the main shock. Our results from recording atmospheric and ionospheric conditions during the earthquake indicate the presence of anomalies in the atmosphere and ionospheres occurring consistently over regions of maximum stress near the epicenter. Due to their long duration (hours and days) and spatial appearance (only over the Sendai region) these results do not appear to be caused by meteorological or magnetic activity. They reveal the existence of atmospheric and ionospheric phenomena occurring prior to the earthquake, which indicates new evidence of a distinct coupling between the lithosphere and atmosphere/ionosphere. Similar results have been reported before the catastrophic events in Chile (M8.8, 2010), Italy (M6.3, 2009) and Sumatra (M9.3, 2004).

Ouzonounov, D.↗

Multi Modality Brain Mapping System (MBMS) Using Artificial Intelligence and Pattern Recognition

A Multimodality Brain Mapping System (MBMS), comprising one or more scopes (e.g., microscopes or endoscopes) coupled to one or more processors, wherein the one or more processors obtain training data from one or more first images and/or first data, wherein one or more abnormal regions and one or more normal regions are identified; receive a second image captured by one or more of the scopes at a later time than the one or more first images and/or first data and/or captured using a different imaging technique; and generate, using machine learning trained using the training data, one or more viewable indicators identifying one or abnormalities in the second image, wherein the one or more viewable indicators are generated in real time as the second image is formed. One or more of the scopes display the one or more viewable indicators on the second image.

Kateb, Babak↗

Cardiovascular Disease Outcomes Among the NASA Astronaut Corps

BACKGROUND: Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in spaceflight activities are associated with changes in the cardiovascular system such as decreased carotid artery distensibility and decreased ventricular mass which may lead to an increased risk of cardiovascular disease. Additionally, astronauts who travel into space multiple times or for longer durations may be at an increased risk across their lifespan. To that end, the purpose of this study was to determine the incidence of common cardiovascular disease (CVD) outcomes among the NASA astronaut corps during their active career and through retirement. METHODS: Cardiovascular disease outcomes were defined as reports of any of the following: myocardial infarction (MI), revascularization procedures (coronary artery bypass graft surgery [CABG] or percutaneous coronary intervention [PCI]), hypertension, stroke or transient ischemic attack [TIA], heart failure, or total CVD (as defined by the AHA - combined outcome of MI, Angina Pectoris, heart failure, stroke, and hypertension). Each outcome was identified individually from review of NASA's Electronic Medical Record (EMR), EKG reports, and death certificates using ICD-9 codes as well as string searches of physician notes of astronaut exams that occurred between 1959 and 2016. RESULTS: Of 338 NASA astronauts selected as of 2016, 9 reported an MI, 12 reported a revascularization procedure, (7 PCI and 5 CABG), 4 reported Angina (without MI), 5 reported heart failure, 9 reported stroke/TIA, and 96 reported hypertension. Total CVD was reported in 105 astronauts. No astronaut who had an MI or revascularization procedure flew a spaceflight mission following the event. All MI, revascularization, and stroke events occurred in male astronauts. When reviewing astronaut ECG reports, abnormal ECG reports were found in only 8% of records (n=430) and mainly among retired astronauts (82%), with marked sinus bradycardia being the reason for the abnormal classification.

Charvat, Jacqueline M.↗

Impact of Recent Climate Extremes on Mosquito-borne Disease Transmission in Kenya

Climate change and variability influence temperature and rainfall, which impact vector abundance and the dynamics of vector-borne disease transmission. Climate change is projected to increase the frequency and intensity of extreme climate events. Mosquito-borne diseases, such as dengue fever, are primarily transmitted by Aedes aegypti mosquitoes. Freshwater availability and temperature affect dengue vector populations via a variety of biological processes and thus influence the ability of mosquitoes to effectively transmit disease. However, the effect of droughts, floods, heat waves, and cold waves is not well understood. Using vector, climate, and dengue disease data collected between 2013 and 2019 in Kenya, this retrospective cohort study aims to elucidate the impact of extreme rainfall and temperature on mosquito abundance and the risk of arboviral infections. To define extreme periods of rainfall and land surface temperature (LST), we calculated monthly anomalies as deviations from long-term means (1983–2019 for rainfall, 2000–2019 for LST) across four study locations in Kenya. We classified extreme climate events as the upper and lower 10% of these calculated LST or rainfall deviations. Monthly Ae. aegypti abundance was recorded in Kenya using four trapping methods. Blood samples were also collected from children with febrile illness presenting to four field sites and tested for dengue virus using an IgG enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). We found that mosquito eggs and adults were significantly more abundant one month following an abnormally wet month. The relationship between mosquito abundance and dengue risk follows a non-linear association. Our findings suggest that early warnings and targeted interventions during periods of abnormal rainfall and temperature, especially flooding, can potentially contribute to reductions in risk of viral transmission

Aedes aegypti mosquitoes↗

The Detection of 6.9 µm Emission Features in the Infrared Spectra of IRAS 04296+3429, IRAS 05341+0852, IRAS 22272+5435: Evidence for the Presence of Hn-PAHs in Post AGB Stars

Polycyclic aromatic hydrocarbons (PAHs) are generally believed to be ubiquitous in space and responsible for numerous telltale interstellar infrared emission bands. In Sandford et al., (2013), we suggested that polycyclic aromatic hydrocarbons with excess hydrogenation at their periphery (Hn-PAHs) may be an important subclass of these molecules in some astrophysical environments. These molecules are candidates to explain objects with anomalously large 3.4 μm features, which are presumed to be associated with the aliphatic C—H stretching vibrations of the excess hydrogen. In that work, we suggest that for Hn-PAHs to be a viable candidate as the source for this 3.4 μm feature, we must also expect to observe methylene scissoring modes at 6.9 μm. In this work, we continue to develop the Hn-PAH hypothesis with a focus on the 6.9 μm feature. We also present some new observations of three post-asymptotic giant branch (post- AGB) objects with abnormally large 3.4 μm features, IRAS 04296+3429, IRAS 05341+0852, IRAS 22272+5435, in addition to one post-AGB object with normal PAH emissions, IRAS 20000+3239. These observations were made using the FORCAST instrument in grism mode on the Stratospheric Observatory for Infrared Astronomy (SOFIA) aircraft (Adams et al. 2010) and demonstrate the presence of a 6.9 μm feature for the three objects with abnormally large 3.4 μm features and no detectable 6.9 μm feature for the normal PAH emitter. These results are consistent with the hypothesis that Hn-PAHs are a possible source of these infrared emission bands.

ISM↗

Dynamic concurrent learning method to neutralize cyber attacks and faults for industrial asset monitoring nodes

Input signals may be received from monitoring nodes of the industrial asset, each input signal comprising time series data representing current operation. A neutralization engine may transform the input signals into feature vectors in feature space, each feature vector being associated with one of a plurality of overlapping batches of received input signals. A dynamic decision boundary may be generated based on the set of feature vectors, and an abnormal state of the asset may be detected based on the set of feature vectors and a predetermined static decision boundary. An estimated neutralized value for each abnormal feature value may be calculated based on the dynamic decision boundary and the static decision boundary such that a future set of feature vectors will be moved with respect to the static decision boundary. An inverse transform of each estimated neutralized value may be performed to generate neutralized signals comprising time series data that are output.

97 MATHEMATICS AND COMPUTING↗

Enhancing the Operational Resilience of Advanced Reactors with Digital Twins by Recurrent Neural Networks

Because of a lack of operation data during abnormal and accident scenarios, along with the existence of uncertainty in the evaluation model for transient and accident analysis, the established abnormal and emergency operating procedures can be biased in characterizing the reactor states and ensuring operational resilience. To improve state awareness and ensure operational flexibility for minimizing effects on the system due to anomaly, digital twin (DT) technology is suggested to support operator's decision-making by effectively extracting and using knowledge of the current and future plant states from the knowledge base. To demonstrate DT's capability for recovering the complete states of reactors and for predicting the future reactor behaviors, this paper develops and assesses both the diagnosis and prognosis DTs in a nearly autonomous management and control system for an Experimental Breeder Reactor-II simulator during different loss-of-flow scenarios.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Dynamic, resilient virtual sensing system and shadow controller for cyber-attack neutralization

An industrial asset may have monitoring nodes (e.g., sensor or actuator nodes) that generate current monitoring node values. An abnormality detection and localization computer may receive the series of current monitoring node values and output an indication of at least one abnormal monitoring node that is currently being attacked or experiencing a fault. An actor-critic platform may tune a dynamic, resilient state estimator for a sensor node and output tuning parameters for a controller that improve operation of the industrial asset during the current attack or fault. The actor-critic platform may include, for example, a dynamic, resilient state estimator, an actor model, and a critic model. According to some embodiments, a value function of the critic model is updated for each action of the actor model and each action of the actor model is evaluated by the critic model to update a policy of the actor-critic platform.

Roychowdhury, Subhrajit↗

Developing IEEE Std 2800-Compliant Algorithms for Transmission-Connected Inverter-Based Resources

This study addresses the compliance of Inverter-based Resources (IBRs) with IEEE Standard 2800, a leading standard that defines interconnection and interoperability requirements for IBRs integrated into transmission systems. Focusing on abnormal grid scenarios, the research evaluates the specific demands on IBRs, proposing a controller development framework for abnormal grid conditions. This framework caters to maintaining ride-through operation in line with IEEE Std 2800, alongside managing currents during voltage ride-through scenarios. The effectiveness of this proposed controller framework is rigorously validated through case studies, employing a MATLAB/Simulink model of an IBR to test its performance under diverse grid fault conditions, ensuring the IBRs' alignment with standard requirements and their robust performance in enhancing grid reliability.

grid↗

Systems, methods, and devices for failure detection of one or more energy storage devices

An energy storage device management system can include a management portion for charging/discharging an energy storage device and an ultrasound interrogation portion for passing ultrasound energy through the energy storage device during charge/discharge cycles. A memory stores a stream of capture data instances derived from ultrasound energy exiting the energy storage device and baseline ultrasound data instances corresponding with the energy storage device during normal charging/discharging thereof. A processor can compare each capture data instance with the baseline ultrasound data and detect abnormal operating states of the energy storage device. A warning system can issue a notification when abnormal operating states are detected.

Kowalski, Jeffrey A.↗

Sequence-Based Anomaly Detection in Critical Infrastructure Networks

United States critical infrastructure faces new cyber threats from adversarial nation-state actors in the form of malware-free attacks. Traditional cybersecurity techniques use rules-based methods to identify indicators of compromise on networks, often missing these sophisticated attacks. Our approach leverages multiple state of the art machine learning models in a pipeline to identify abnormal network events through sequential analysis. We combine both device and packet-level information into individual events to characterize anomalous network actions. The model is trained and tested on real network traffic from the Idaho National Lab High Performance Computing (HPC) with greater than 98% precision. It is capable of flagging malicious tactics used by adversaries in malware-free attacks, severe changes to the network, and abnormal user activity by network devices.

99 - GENERAL AND MISCELLANEOUS↗