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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 325 records · Page 18

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.

59 BASIC BIOLOGICAL SCIENCES↗

Adaptive anomaly detection for identifying attacks in cyber-physical systems: A systematic literature review

Modern cyberattacks in cyber-physical systems (CPS) rapidly evolve and cannot be deterred effectively with most current methods, which focus on characterizing past threats. Adaptive anomaly detection (AAD) is among the most promising techniques to detect evolving cyberattacks, with an emphasis on fast data processing and model adaptation. AAD has been researched extensively; however, to the best of our knowledge, our work is the first systematic literature review (SLR) on current research in this field. We present a comprehensive SLR, gathering 397 relevant papers and systematically analyzing 65 of them (47 research and 18 survey papers) on AAD in CPS from 2013 to November 2023. We introduce a novel taxonomy considering attack types, CPS application, learning paradigm, data management, and algorithms. Our findings show that most studies addressed either model adaptation or data processing, but rarely both simultaneously. This indicates a research gap in fully adaptive solutions. We also categorize algorithms, datasets, and attack characteristics, and summarize strengths and weaknesses across the literature. Our review provides a structured and accessible reference for researchers and practitioners, offering insights into key trends and highlighting limitations in current approaches. Finally, we outline several future research directions, including the need for integrated real-time processing and adaptive learning, explainability, and uncertainty quantification in AAD for CPS.

Adaptation↗

Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer

Hypofractionated radiation therapy can be used to treat patients with muscle-invasive bladder cancer unable to have radical therapy. Toxicity is a key concern, but adaptive plan-of the day (POD) image-guided radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Challenges in cell transplantation for muscular dystrophy

For decades now, cell transplantation has been considered a possible therapeutic strategy for muscular dystrophy, but failures have largely outnumbered success or at least encouraging outcomes. }In this review we will briefly recall the history of cell transplantation, discuss the peculiar features of skeletal muscle, and dystrophic skeletal muscle in particular, that make the procedure complicated and inefficient. As there are many recent and exhaustive reviews on the various myogenic cell types that have been or will be transplanted, we will only briefly describe them and refer the reader to these reviews. }Finally, we will discuss possible strategies to overcome the hurdles that prevent biological efficacy and hence clinical success.

60 APPLIED LIFE SCIENCES↗

Circulating SARS-CoV-2 + megakaryocytes are associated with severe viral infection in COVID-19

Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating megakaryocytes in a large cohort of inpatients with COVID-19 and correlated the subpopulation frequencies with clinical outcomes. Using peripheral blood, we show that megakaryocytes are increased in the systemic circulation in COVID-19, and we identify and validate S100A8/A9 as a defining marker of megakaryocyte dysfunction. We further reveal a subpopulation of S100A8/A9 + megakaryocytes that contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein and RNA. Using flow cytometry of peripheral blood and in vitro studies on SARS-CoV-2–infected primary human megakaryocytes, we demonstrate that megakaryocytes can transfer viral antigens to emerging platelets. Mechanistically, we show that SARS-CoV-2–containing megakaryocytes are nuclear factor κB (NF-κB)-activated, via p65 and p52; express the NF-κB–mediated cytokines interleukin-6 (IL-6) and IL-1β; and display high surface expression of Toll-like receptor 2 (TLR2) and TLR4, canonical drivers of NF-κB. In a cohort of 218 inpatients with COVID-19, we correlate frequencies of megakaryocyte subpopulations with clinical outcomes and show that SARS-CoV-2–containing megakaryocytes are a strong risk factor for mortality and multiorgan injury, including respiratory failure, mechanical ventilation, acute kidney injury, thrombotic events, and intensive care unit admission. Furthermore, we show that SARS-CoV-2 + megakaryocytes are present in lung and brain autopsy tissues from deceased donors who had COVID-19. To our knowledge, this study offers the first evidence implicating SARS-CoV-2 + peripheral megakaryocytes in severe disease and suggests that circulating megakaryocytes warrant investigation in inflammatory disorders beyond COVID-19.

60 APPLIED LIFE SCIENCES↗

Tunable White Light for Elders (TWLITE): A Protocol Demonstrating Feasibility and Acceptability for Deployment, Remote Data Collection, and Analysis of a Home-Based Lighting Intervention in Older Adults

Sleep disturbances are common in older adults and may contribute to disease progression in certain populations (e.g., Alzheimer’s disease). Light therapy is a simple and cost-effective intervention to improve sleep. Primary barriers to light therapy are: (1) poor acceptability of the use of devices, and (2) inflexibility of current devices to deliver beyond a fixed light spectrum and throughout the entirety of the day. However, dynamic, tunable lighting integrated into the native home lighting system can potentially overcome these limitations. Herein, we describe our protocol to implement a whole-home tunable lighting system installed throughout the homes of healthy older adults already enrolled in an existing study with embedded home assessment platforms (Oregon Center for Aging & Technology—ORCATECH). Within ORCATECH, continuous data on room location, activity, sleep, and general health parameters are collected at a minute-to-minute resolution over years of participation. This single-arm longitudinal protocol collected participants’ light usage in addition to ORCATECH outcome measures over a several month period before and after light installation. The protocol was implemented with four subjects living in three ORCATECH homes. Technical/usability challenges and feasibility/acceptability outcomes were explored. The successful implementation of our protocol supports the feasibility of implementing and integrating tunable whole-home lighting systems into an automated home-based assessment platform for continuous data collection of outcome variables, including long-term sleep measures. Challenges and iterative approaches are discussed. This protocol will inform the implementation of future clinical intervention trials using light therapy in patients at risk for developing Alzheimer’s disease and related conditions.

60 APPLIED LIFE SCIENCES↗

Graph-based featurization methods for classifying small molecule compounds

For over a decade, drug-induced liver injury (DILI) has posed significant drawbacks in the synthesis and development of drugs and remains a consequential concern. With finite success within the existing preclinical models, DILI is one of the main causes of drug withdrawal or termination from the market. Particularly, this withdrawal occurs during the late stages of drug development (Kullak-Ublick, 2017). Since DILI is difficult to diagnose and treat, it has become an obstacle in the drug production market that in turn affects clinicians, pharmaceutical companies, and consumers. We propose a method for learning features of DILI-positive drugs based on the graphical relationships and patterns they possess within a network of biological databases. We also train various statistical and machine learning models on these learned features in order to classify the drugs as DILI-positive or negative. Our methods include Random Forest, Neural networks, and logistic regression classification. We utilize labeled DILI-positive and DILI-negative datasets, which were developed by the FDA and the National center for toxicological research, as well as additional literature datasets (Thakkar, 2020) in order to validate our results and assess our featurization and model accuracy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight

Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only approximately 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A (a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1). significantly smaller pressor responses to phenylephrine both before and after flight; 2). significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3). significantly greater norepinephrine release with tyramine on landing day; and 4). significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired.

Clinical Trial↗

Age affects severity of venous gas emboli on decompression from 14.7 to 4.3 psia

INTRODUCTION: Variables that define who we are, such as age, weight and fitness level influence the risk of decompression sickness (DCS) and venous gas emboli (VGE) from diving and aviation decompressions. We focus on age since astronauts that perform space walks are approximately 10 yr older than our test subjects. Our null hypothesis is that age is not statistically associated with the VGE outcomes from decompression to 4.3 psia. METHODS: Our data are from 7 different NASA tests where 188 men and 50 women performed light exercise at 4.3 psia for planned exposures no less than 4 h. Prebreathe (PB) time on 100% oxygen ranged from 150-270 min, including ascent time, with exercise of different intensity and length being performed during the PB in four of the seven tests with 150 min of PB. Subjects were monitored for VGE in the pulmonary artery using a Doppler ultrasound bubble detector for a 4-min period every 12 min. There were six design variables; the presence or absence of lower body adynamia and five PB variables; plus five concomitant variables on physical characteristics: age, weight height, body mass index, and gender that were available for logistic regression (LR). We used LR models for the probability of DCS and VGE, and multinomial logit (ML) models for the probability of Spencer VGE Grades 0-IV at exposure times of 61, 95, 131, 183 min, and for the entire exposure. RESULTS: Age was significantly associated with VGE in both the LR and ML models, so we reject the null hypothesis. Lower body adynamia was significant for all responses. CONCLUSIONS: Our selection of tests produced a wide range of the explanatory variables, but only age, lower body adynamia, height, and total PB time was helpful in various combinations to model the probability of DCS and VGE.

Clinical Trial↗

Characteristics of covert and overt visual orienting: Evidence from attentional and oculomotor capture

Five visual search experiments found oculomotor and attentional capture consistent with predictions of contingent orienting, contrary to claims that oculomotor capture is purely stimulus driven. Separate saccade and attend-only conditions contained a color target appearing either singly, with an onset or color distractor, or both. In singleton mode, onsets produced oculomotor and attentional capture. In feature mode, capture was absent or greatly reduced, providing evidence for top-down modulation of both types of capture. Although attentional capture by color abstractors was present throughout, oculomotor capture by color occurred only when accompanied by transient change, providing evidence for a dissociation between oculomotor and attentional capture. Oculomotor and attentional capture appear to be mediated by top-down attentional control settings, but transient change may be necessary for oculomotor capture. ((c) 2003 APA, all rights reserved).

Clinical Trial↗

Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy

Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO(2)) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO(2) occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO(2) and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices.

NASA Program Biomedical Research and Countermeasur↗

Sensorimotor aspects of high-speed artificial gravity: II. The effect of head position on illusory self motion

The effects of cross-coupled stimuli on the semicircular canals are shown to be influenced by the position of the subject's head with respect to gravity and the axis of rotation, but not by the subject's head position relative to the trunk. Seventeen healthy subjects made head yaw movements out of the horizontal plane while lying on a horizontal platform (MIT short radius centrifuge) rotating at 23 rpm about an earth-vertical axis. The subjects reported the magnitude and duration of the illusory pitch or roll sensations elicited by the cross-coupled rotational stimuli acting on the semicircular canals. The results suggest an influence of head position relative to gravity. The magnitude estimation is higher and the sensation decays more slowly when the head's final position is toward nose-up (gravity in the subject's head x-z-plane) compared to when the head is turned toward the side (gravity in the subject's head y-z-plane). The results are discussed with respect to artificial gravity in space and the possible role of pre-adaptation to cross-coupled angular accelerations on earth.

Non-NASA Center↗

Identifying head-trunk and lower limb contributions to gaze stabilization during locomotion

The goal of the present study was to determine how the multiple, interdependent full-body sensorimotor subsystems respond to a change in gaze stabilization task constraints during locomotion. Nine subjects performed two gaze stabilization tasks while walking at 6.4 km/hr on a motorized treadmill: 1) focusing on a central point target; 2) reading numeral characters; both presented at 2 m in front at the level of their eyes. While subjects performed the tasks we measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, tibia and foot, accelerations along the vertical axis at the head and the tibia, and the vertical forces acting on the support surface. We tested the hypothesis that with the increased demands placed on visual acuity during the number recognition task, subjects would modify full-body segmental kinematics in order to reduce perturbations to the head in order to successfully perform the task. We found that while reading numeral characters as compared to the central point target: 1) compensatory head pitch movement was on average 22% greater despite the fact that the trunk pitch and trunk vertical translation movement control were not significantly changed; 2) coordination patterns between head and trunk as reflected by the peak cross correlation between the head pitch and trunk pitch motion as well as the peak cross correlation between the head pitch and vertical trunk translation motion were not significantly changed; 3) knee joint total movement was on average 11% greater during the period from the heel strike event to the peak knee flexion event in stance phase of the gait cycle; 4) peak acceleration measured at the head was significantly reduced by an average of 13% in four of the six subjects. This was so even when the peak acceleration at the tibia and the transmission of the shock wave at heel strike (measured by the peak acceleration ratio of the head/tibia and the time lag between the tibial and head peak accelerations) remained unchanged. Taken together these results provide further evidence that the full body contributes to gaze stabilization during locomotion, and that its different functional elements can be modified online to contribute to gaze stabilization for different visual task constraints.

NASA Center JSC↗

Context-specific adaptation of saccade gain in parabolic flight

Previous studies established that vestibular reflexes can have two adapted states (e.g., gains) simultaneously, and that a context cue (e.g., vertical eye position) can switch between the two states. Our earlier work demonstrated this phenomenon of context-specific adaptation for saccadic eye movements: we asked for gain decrease in one context state and gain increase in another context state, and then determined if a change in the context state would invoke switching between the adapted states. Horizontal and vertical eye position and head orientation could serve, to varying degrees, as cues for switching between two different saccade gains. In the present study, we asked whether gravity magnitude could serve as a context cue: saccade adaptation was performed during parabolic flight, which provides alternating levels of gravitoinertial force (0 g and 1.8 g). Results were less robust than those from ground experiments, but established that different saccade magnitudes could be associated with different gravity levels.

Clinical Trial↗