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At least 163 records · Page 9

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NASA NTRS2003

Resolution of sensory ambiguities for gaze stabilization requires a second neural integrator

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

Non-NASA Center↗

NASA NTRS1972

Direction-specific adaptation effects acquired in a slow rotation room.

Thirty-eight subjects were required to execute 120 head movements in a slow rotation room at each 1-rpm increase in velocity of the room between 0 and 6 rpm and, after a single-step gradual return to zero velocity, execute 120 head movements either immediately after return or after delay periods varying from 1 to 24 hours unless, at any time, more than mild symptoms of motion sickness were elicited. A second stress profile differed by the sequential addition of an incremental adaptation schedule (identical to the first) in which the direction of rotation was reversed. The experimental findings demonstrated the acquisition of direction-specific adaptation effects that underwent spontaneous decay with a short time constant (hours). With their disappearance a nondirection-specific adaptation was revealed with a long-time constant (days). Speculations are presented which could account for the simultaneous acquisition of short-term and long-term adaptation effects.

Graybiel, A.↗

NASA NTRS1972

Direction-specific adaptation effects acquired in a slow rotation room

Thirty-eight subjects were required to execute 120 head movements in a slow rotation room at each 1-rpm increase in velocity of the room between 0 and 6 rpm and, after a single-step gradual return to zero velocity, execute 120 head movements either immediately after the return or after delay periods varying from 1 to 24 hours unless, at any time, more than mild symptoms of motion sickness were elicited. A second stress profile differed by the sequential addition of an incremental adaptation schedule in which the direction of rotation was reversed. The experimental findings demonstrated the acquisition of direction-specific adaptation effects that underwent spontaneous decay with a short time constant (hours). Speculations are presented which could account for the simultaneous acquisition of short-term and long-term adaptation effects. The findings support the theory that motion sickness, although a consequence of vestibular stimulation, has its immediate origin in nonvestibular systems, implying a faculative or temporary linkage between the vestibular and nonvestibular systems.

Graybiel, A.↗

NASA NTRSDate not supplied

Novel Approach to Simulating Diagnostic Capabilities in Medical Resource Risk Assessment

Diagnostics represent a key subset of medical resources considered for helping mitigate and control spaceflight medical risk. Historically, when modeling the medical risk domain for spaceflight, diagnostic resources have been handled like any other medical resource used for treatment. That is to say, the resource being unavailable will result in the related condition having suboptimal treatment outcomes. However in the real world, should a diagnostic resource be unavailable, a more analogous effect would be that the condition might be misdiagnosed, and thus inappropriate treatment applied. This talk presents an alternative means of representing diagnostic resources within the Medical Extensible Dynamic Probabilistic Risk Assessment Tool (MEDPRAT) that can simulate the effect both in risk, resource consumption, and competition for resources of a missing or depleted diagnostic. The scenario where a differential diagnosis may not be possible for abdominal conditions that use an ultrasound machine as a diagnostic tool is considered. Two approaches for modeling the effect of not having a diagnostic capability on the medical system are demonstrated. In the “simple” approach, it is assumed that any abdominal condition requiring the ultrasound machine for diagnosis is mis-diagnosed and treated as an appendicitis. This is represented by replacing the treatment for the affected conditions with the treatment for appendicitis, thereby changing the optimized medical set available for treatment for the remainder of the mission. In the “complex” approach, MEDPRAT treatment clusters are utilized to capture and represent overlapping treatment between the misdiagnosed condition and appendicitis. This elicits both the effect that inappropriate treatment is applied, resulting in wasted resource consumption, and that treatment which was truly needed for the misdiagnosed condition was not applied, which reduces the treatment effectiveness. In this talk, results comparing the simple and complex diagnostic capability approach to a baseline where the diagnostic is treated as a traditional resource is presented. Either approach provides an option for a more analogous representation of diagnostic resources and provides insight into how the modeled spaceflight medical resources and outcomes change when that diagnostic is unavailable.

C. M. Gasiewski↗

DOE OSTI2021

Gap Assessment on Sensors and Instrumentation for Advanced Reactors

The Sensor Technologies for Advanced Reactors Virtual Workshop—sponsored by the Gateway for Accelerated Innovation in Nuclear (GAIN), the Electric Power Research Institute, and the Nuclear Energy Institute—was held to exchange information on sensors and sensor technologies of interest to advanced nuclear technology developers, commercial instrument suppliers, and sensor researchers from Department of Energy (DOE) national laboratories, universities, and industry. The workshop objectives were to discuss measurement requirements and sensor needs for advanced reactor concepts, understand current national laboratory capabilities and accelerated development approaches for sensors and instrumentation, and identify gaps so as to inform applicable DOE Office of Nuclear Energy (DOE-NE) research programs. Due to the complexity of holding group discussions on individual gaps, a survey was sent to workshop participants, and personalized one-on-one feedback sessions were held to elicit additional information. Summaries of these sessions are provided in this gap assessment report.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

NASA NTRS2006

Generic Environment for Simulating Launch Operations

GEM-FLO (A Generic Simulation Environment for Modeling Future Launch Operations) is a computer program that facilitates creation of discrete-event simulation models of ground processes in which reusable or expendable launch vehicles (RLVs) are prepared for flight. GEM-FLO includes a component, developed in Visual Basic, that generates a graphical user interface (GUI) and a component, developed in the Arena simulation language, that creates a generic discrete-event simulation model. Through the GUI, GEM-FLO elicits RLV design information from the user. The design information can include information on flight hardware elements, resources, and ground processes. GEM-FLO translates the user s responses into mathematical variables and expressions that populate the generic simulation model. The variables and expressions can represent processing times, resource capacities, status variables, and other process parameters needed to configure a simulation model that reflects the ground processing flow and requirements of a specific RLV. Upon execution of the model, GEMFLO puts out data on many measures of performance, including the flight rate, turnaround time, and utilization of resources. This information can serve as the basis for determining whether design goals can be met, and for comparing characteristics of competing RLV designs

Steele, Martin↗

NASA NTRS2016

Relationships Between Vestibular Measures as Potential Predictors for Spaceflight Sensorimotor Adaptation

Introduction: During space exploration missions astronauts are exposed to a series of novel sensorimotor environments, requiring sensorimotor adaptation. Until adaptation is complete, sensorimotor decrements occur, affecting critical tasks such as piloted landing or docking. Of particularly interest are locomotion tasks such as emergency vehicle egress or extra-vehicular activity. While nearly all astronauts eventually adapt sufficiently, it appears there are substantial individual differences in how quickly and effectively this adaptation occurs. These individual differences in capacity for sensorimotor adaptation are poorly understood. Broadly, we aim to identify measures that may serve as pre-flight predictors of and individual's adaptation capacity to spaceflight-induced sensorimotor changes. As a first step, since spaceflight is thought to involve a reinterpretation of graviceptor cues (e.g. otolith cues from the vestibular system) we investigate the relationships between various measures of vestibular function in humans. Methods: In a set of 15 ground-based control subjects, we quantified individual differences in vestibular function using three measures: 1) ocular vestibular evoked myogenic potential (oVEMP), 2) computerized dynamic posturography and 3) vestibular perceptual thresholds. oVEMP responses are elicited using a mechanical stimuli approach. Computerized dynamic posturography was used to quantify Sensory Organization Tests (SOTs), including SOT5M which involved performing pitching head movements while balancing on a sway-reference support surface with eyes closed. We implemented a vestibular perceptual threshold task using the tilt capabilities of the Tilt-Translation Sled (TTS) at JSC. On each trial, the subject was passively roll-tilted left ear down or right ear down in the dark and verbally provided a forced-choice response regarding which direction they felt tilted. The motion profile was a single-cycle sinusoid of angular acceleration with a duration of 5 seconds (frequency of 0.2 Hz), which was selected as it requires sensory integration of otolith and semicircular canal cues. Stimuli direction was randomized and magnitude was determined using an adaptive sampling procedure. One hundred trials were provided and each subject's responses were fit with a psychometric curve to estimate the subject's threshold. Results: Roll tilt perceptual thresholds at 0.2 Hz ranged from 0.5 degrees to 1.82 degrees across the 15 subjects (geometric mean of 1.04 degrees), consistent with previous studies. The inter-individual variability in thresholds may be able to help explain individual differences observed in sensorimotor adaptation to spaceflight. Analysis is ongoing for the oVEMPS and computerized dynamic posturography to identify relationships between the various vestibular measures. Discussion: Predicting individual differences in sensorimotor adaptation is critical both for the development of personalized countermeasures and mission planning. Here we aim to develop a basis of vestibular tests and parameters which may serve as predictors of individual differences in sensorimotor adaptability through studying the relationship between these measures.

Clark, T. K.↗

NASA NTRS1974

Effects of background event rate and critical signal amplitude on vigilance performance

Subjects monitored a display consisting of the repetitive presentation of pairs of movements of a bar of light. A neutral background event, for which no overt response was required, was a double deflection of 24 mm. The critical signal for detection was a longer deflection in the second movement within an event. Detection probability was greater for incremental excursions of 33% relative to 8.3% of the base movement. This effect was enhanced twofold when the event rate in which the signals were embedded was 21 as compared to 6 events/min. The results are considered in terms of the elicited observing rate hypothesis proposed by Jerison (1970).

Metzger, K. R.↗

DOE OSTI2023

Whole‐Cell MALDI‐ToF MS Coupled with Untargeted Metabolomics Facilitates Investigations of Microbial Chemical Interactions

Abstract The emergence of drug‐resistant pathogens necessitates the development of new countermeasures. In this regard, the introduction of probiotics to directly attack or competitively exclude pathogens presents a useful strategy. Application of this approach requires an understanding of how a probiotic and its target pathogen interact. A key means of probiotic‐pathogen interaction involves the production of small molecules called natural products (NPs). Here, we report the use of whole‐cell matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐ToF) mass spectrometry to characterize NP production by candidate probiotics (mouse airway microbiome isolates) when co‐cultured with the respiratory pathogen Burkholderia . We found that a Bacillus velezensis strain inhibits growth of and elicits NP production by Burkholderia thailandensis . Dereplication of known NPs detected in the metabolome of this B. velezensis strain suggests that a previously unannotated bioactive compound is involved. Thus, we present the use of whole‐cell MALDI as a broadly applicable method for screening the NP composition of microbial co‐cultures; this can be combined with other ‐omics methods to characterize probiotic‐pathogen and other microbe‐microbe interactions.

Aiosa, Nicole↗

DOE OSTI2023

Automated classification of big X-ray diffraction data using deep learning models

Abstract In current in situ X-ray diffraction (XRD) techniques, data generation surpasses human analytical capabilities, potentially leading to the loss of insights. Automated techniques require human intervention, and lack the performance and adaptability required for material exploration. Given the critical need for high-throughput automated XRD pattern analysis, we present a generalized deep learning model to classify a diverse set of materials’ crystal systems and space groups. In our approach, we generate training data with a holistic representation of patterns that emerge from varying experimental conditions and crystal properties. We also employ an expedited learning technique to refine our model’s expertise to experimental conditions. In addition, we optimize model architecture to elicit classification based on Bragg’s Law and use evaluation data to interpret our model’s decision-making. We evaluate our models using experimental data, materials unseen in training, and altered cubic crystals, where we observe state-of-the-art performance and even greater advances in space group classification.

Chemistry↗

DOE OSTI2023

Electrophysiological Signatures of Visual Recognition Memory across All Layers of Mouse V1

In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared with novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli. SRP is dependent on NMDA receptors (NMDARs) and has been hypothesized to reflect potentiation of thalamocortical (TC) synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells. To shed light on where and how SRP is induced and expressed in male and female mice, the present study had three related aims: (1) to confirm that NMDAR are required specifically in glutamatergic principal neurons of V1, (2) to investigate the consequences of deleting NMDAR specifically in L6, and (3) to use translaminar electrophysiological recordings to characterize SRP expression in different layers of V1. We find that knock-out (KO) of NMDAR in L6 principal neurons disrupts SRP. Current-source density (CSD) analysis of the VEP depth profile shows augmentation of short latency current sinks in layers 3, 4, and 6 in response to phase reversals of familiar stimuli. Multiunit recordings demonstrate that increased peak firing occurs in response to phase reversals of familiar stimuli across all layers, but that activity between phase reversals is suppressed. Together, these data reveal important aspects of the underlying phenomenology of SRP and generate new hypotheses for the expression of experience-dependent plasticity in V1. SIGNIFICANCE STATEMENT Repeated exposure to stimuli that portend neither reward nor punishment leads to behavioral habituation, enabling organisms to dedicate attention to novel or otherwise significant features of the environment. The neural basis of this process, which is so often dysregulated in neurologic and psychiatric disorders, remains poorly understood. Learning and memory of stimulus familiarity can be studied in mouse visual cortex by measuring electrophysiological responses to simple phase-reversing grating stimuli. The current study advances knowledge of this process by documenting changes in visual evoked potentials (VEPs), neuronal spiking activity, and oscillations in the local field potentials (LFPs) across all layers of mouse visual cortex. In addition, we identify a key contribution of a specific population of neurons in layer 6 (L6) of visual cortex.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

Plant metacaspases orchestrate wound‐induced pathways for immunity and tissue regeneration

Wounding in plants elicits immunity and tissue repair, but how these responses are coordinated has yet to be elucidated. While plant metacaspases resemble animal caspases in structure and immunity induction, their role in tissue repair and regeneration is unknown. Using Arabidopsis mutants lacking type II metacaspases AtMC4 or AtMC9, we found that the majority of the highly induced, wound-responsive genes in Arabidopsis thaliana are suppressed by the loss of AtMC4, while AtMC9 plays an auxiliary role in defense activation. Specifically, AtMC4, but not AtMC9, is required for the activation of genes involved in tissue repair, such as the developmental regulator WOX5, as well as for root regeneration from excised leaves. Instead, AtMC9 mediates the repression of a subset of basal immunity genes, which modifies the wound-activated defense response from that induced by molecular patterns such as the bacterial flg22 elicitor. Our results thus reveal a conserved protease module that coordinates plant defense and tissue repair upon wounding. They could be new targets to improve crop performance and plant transformation protocols that involve tissue wounding before transgenic plant selection and regeneration. The groups of genes with distinctive requirements for the two metacaspases could provide markers to dissect how these specialized proteases affect different response pathways that underpin the multifaceted wounding response.

54 ENVIRONMENTAL SCIENCES↗

NASA NTRS2023

Orion Cabin Lighting System: Filter Workaround for Maintaining Crew Circadian Entrainment

Introduction: Suboptimal crew circadian entrainment (CCE) is common and results in cumulative fatigue and reduced cognitive function. This may promote use of psychostimulants and hypnotics. The Orion Cabin Lighting System (OCLS) consists of 15 dimmable lamps circuited to several zones. The OCLS monochromatic white lamp design is insufficient for maintaining CCE. While blue light (480-nm) elicits peak wake-cycle response, it is a powerful disruptor of CCE. We propose OCLS lamp filters (OLFs) as a workaround for maintaining CCE. Methods: Preliminary OLFs testing utilized a tunable-white LED to serve as a baseline lamp in the NASA Lighting Lab’s controlled environment (prototype OCLS lamps were unavailable). Illuminance and spectral irradiances were measured with the NASA Lighting Lab’s spectroradiometer. ConOps is proposed for OLFs. Results: OLFs markedly attenuated 480-nm light and illumination with minimal mass/volume requirements. ConOps includes in-flight deployment of OLFs and reducing OCLS lamp intensity prior to bedtime. Pros: minimal mass/volume, no added power, and a simplistic design. Cons: manual twice-daily articulation of OLFs, undetermined frangibility/flammability/off-gassing and effects on thermal regulation, and untested task illumination or color fidelity in the Orion cabin. Discussion: While OLFs aptly attenuate 480-nm light from our tunable LED lamp in the Lighting Lab’s controlled environment, they remain untested within the Orion cabin on OCLS lamps. Future tests include Orion cabin illumination optimization for appropriate Lux delivery and ensuring task/color fidelity with OLFs deployed. Adequate OCLS cooling should be similarly assessed. Other safety testing includes OLF frangibility/flammability/off-gassing in an enriched-O 2 /hypobaric environment. Together, these data will demonstrate OLFs provide a viable workaround for maintaining CCE further ensuring mission safety and success.

Carlos Rene Dostal↗

NASA NTRS1985

Processing inferences derived from event-related potential measures in a monitoring task

Event-related potentials (ERPs) were recorded from the scalp of subjects as they monitored changing digital readouts for values that went 'out-of-bounds'. Workload was manipulated by varying the number of readouts that were monitored concurrently. The ERPs elicited by changes in the readouts showed long latency positivities that increased in amplitude, not only with the number of readouts monitored, but also with the number of monitored readouts that were 'in danger' of going out-of-bounds. No effects were found due to the number of nonmonitored readouts 'in danger'. This evidence indicates that subjects (1) selectively attended to the monitored readouts and (2) processed the monitored readouts differently as the readouts approached the out-of-bounds levels to which an overt response was required.

Horst, R. L.↗

DOE OSTI2020

Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST

Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST. The inference of the time of infection is a critical parameter in testing the efficacy of clinical interventions in protecting against HIV-1 infection. For example, in clinical trials evaluating the efficacy of passively delivered antibodies (Abs) for preventing infections, accurate time of infection data are essential for discerning levels of the Abs required to confer protection, given the natural Ab decay rate in the human body. In such trials, genetic sequences from early in the infection are regularly sampled from study participants, generally prior to immune selection, when the viral population is still expanding and genetic diversity is low. In this particular setting of early viral growth, the Poisson method is superior to the alternative approach based on coalescent methods. This approach can also be applied in human vaccine trials, where accurate estimates of infection times help ascertain if vaccine-elicited immune protection wanes over time.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2010

NextGen Future Safety Assessment Game

The successful implementation of the next generation infrastructure systems requires solid understanding of their technical, social, political and economic aspects along with their interactions. The lack of historical data that relate to the long-term planning of complex systems introduces unique challenges for decision makers and involved stakeholders which in turn result in unsustainable systems. Also, the need to understand the infrastructure at the societal level and capture the interaction between multiple stakeholders becomes important. This paper proposes a methodology in order to develop a holistic approach aiming to provide an alternative subject-matter expert (SME) elicitation and data collection method for future sociotechnical systems. The methodology is adapted to Next Generation Air Transportation System (NextGen) decision making environment in order to demonstrate the benefits of this holistic approach.

Ancel, Ersin↗

NASA NTRS2011

NextGen Future Safety Assessment Game

Ancel, Ersin↗

DOE OSTI2023

Activation of human STING by a molecular glue-like compound

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.

60 APPLIED LIFE SCIENCES↗