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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina’s HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Is the spatial distribution of brain lesions associated with closed-head injury in children predictive of subsequent development of posttraumatic stress disorder?

PURPOSE: To determine whether there is an association between the spatial distributions of lesions detected at magnetic resonance (MR) imaging of the brain in children, adolescents, and young adults after closed-head injury (CHI) and development of the reexperiencing symptoms of posttraumatic stress disorder (PTSD). MATERIALS AND METHODS: Data obtained in 94 subjects without a history of PTSD as determined by parental interview were analyzed. MR images were obtained 3 months after CHI. Lesions were manually delineated and registered to the Talairach coordinate system. Mann-Whitney analysis of lesion distribution and PTSD status at 1 year (again, as determined by parental interview) was performed, consisting of an analysis of lesion distribution versus the major symptoms of PTSD: reexperiencing, hyperarousal, and avoidance. RESULTS: Of the 94 subjects, 41 met the PTSD reexperiencing criterion and nine met all three PTSD criteria. Subjects who met the reexperiencing criterion had fewer lesions in limbic system structures (eg, the cingulum) on the right than did subjects who did not meet this criterion (Mann-Whitney, P =.003). CONCLUSION: Lesions induced by CHI in the limbic system on the right may inhibit subsequent manifestation of PTSD reexperiencing symptoms in children, adolescents, and young adults. Copyright RSNA, 2002.

Non-NASA Center↗
DOE OSTI2020

A Phenomenological Model for Cavitation

A phenomenological model of cavitation is presented, based on observations that both large relative negative pressures and large negative time derivatives of pressure are required for cavitation onset. We simulated two cavitation experiments to generate cavitation scaling parameters for relative pressure drop and rate of pressure drop. Our results show the model, while simple, is effective at reproducing results from laboratory experiments of cavitation. The parameters were then used in conjunction with a human surrogate computational model to predict, at any position within the head, the probability of intracranial cavitation caused by exposure to a blast event. The results suggest that the magnitude of blast overpressure observed in field data is sufficient to cause intracranial cavitation. Our analysis indicates that the helmeted head, when compared to the unhelmeted head configuration, results in a decrease but not elimination of cavitation exposure. When density functions of cavitation probability versus cumulative brain volume are combined with an injury severity model, the results show helmet efficacy at low and moderate risk levels. However, the convergence of unhelmeted and helmeted probability density functions at high-to-excessive risk thresholds indicates the helmet offers diminishing protection at elevated exposure levels, relative to the unhelmeted baseline. Future investigation and collaboration with neuroscience subject matter experts are needed to contextualize the current computational results. While the present work contributes specific and quantified predictions of intracranial cavitation location and severity, more research is required to apply our results to clinical settings with population-based brain injury subjects and controls. The relationship between our intracranial cavitation predictions with their anticipated clinical sequelae remains a topic in need of exploration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Graph-Based Modeling for the Detection and Tracking of Sarin-Surrogate-Induced Neurotoxicity Using a Human-Relevant, In-Vitro Brain Model

Organophosphorus (OP) nerve agents are a chemical threat to the United States, to the civilian population (e.g., pesticides) and historically weaponized (e.g., sarin) as chemical warfare agents. The unprecedented, accelerated process from “bench-to-bedside” during the SARSCov2 pandemic has made it clear that technology and tools need to be readily available for immediate response. Advances in human organ tissue mimetic systems are a promising technology to evaluate the human-relevant response in vitro for basic and applied research and drug screening. In particular, current brain microphysiological systems (MPS) have the capability to monitor and detect changes in engineered human neural circuit activity. However, current data analytics approaches for these systems lack the granularity to functionally detect and distinguish the different mechanisms that occur in the brain following neurotoxicity, injury, and disease. The goal of this project was to advance the computational analytical capabilities of the brain MPS to detect functional changes in neural circuit structure at different stages of Sarin surrogate-induced neurotoxicity. We developed graph-based models to (1) identify the composition of the neural circuit structure; (2) detect and monitor how this structure changes following sarin-induced neurotoxicity; and (3) evaluate the analytical pipeline using known/promising oxime reactivators. Through experiments on the bMPS where in vitro neuronal cultures were exposed to a sarin surrogate, we demonstrated the capabilities of our computational pipeline to identify different responses in the functional networks of brain cells exposed to low and high concentrations of the nerve agent. We identified a biphasic response of human neural network activity following exposure to a sarin-surrogate that had not been reported in the literature before. The graph-based models and software developed in this project can be used for future studies that leverage the brain MPS technology, such as treatment efficacy assessment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Microstructural Injury to Corpus Callosum and Intrahemispheric White Matter Tracts Correlate With Attention and Processing Speed Decline After Brain Radiation

The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie

Objective: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Results: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrP Sc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Conclusion: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2023

Numerical Investigation of Occupant Injury Risks During A Realistic Transport Aircraft Crash Conditions

Researchers at the National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) have conducted a full-scale crash test of a Fokker F28 MK1000 aircraft to investigate the performance of transport aircraft under realistic crash conditions. This crash test was computationally recreated using finite element (FE) human body models (HBMs) to further explore potential injury risks to occupants and analyze the utilization of HBMs in the aerospace crash environment. The Global Human Body Model Consortium (GHBMC) male 50th percentile occupant detailed model (v6.0) and the Toyota Human Model for Safety (THUMS) male 50th percentile occupant model (v6.1) were selected to be used in the crash simulations. The HBMs were simulated in conditions matching those of anthropomorphic test device (ATD) experiments included within the aircraft cabin during the crash test. Seven occupant locations within the cabin were simulated utilizing each of the models. The models were positioned in a neutral upright posture with hands resting on the legs and the feet contacting the floor. Head, brain, neck, and lumbar vertebra injury metrics were calculated for all trials. Both HBM models required minor modifications to stabilize these simulations. The GHBMC model required added erosion for six parts while the THUMS model only required one in order to complete the full simulation. The THUMS model, however, required a much smaller timestep for stability and therefore took significantly more computational time. In addition the GHBMC model includes integrated instrumentation while the THUMS model requires development and implementation of instrumentation. Both models predicted 100% injury risk for lumbar vertebra fracture in all test conditions. This prediction was in family with high lumbar load values measured by the ATDs during the crash test. The THUMS model consistently predicted lower injury risks than the GHBMC model in all three other metrics varying depending on the crash pulse. Overall, the THUMS model required less modifications to allow for this study. However, the GHBMC models significantly faster run time and integrated instrumentation make it a more intuitive model for this research.

Crashworthiness↗
NASA NTRS2002

Paralysis recovery in humans and model systems

Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

Review↗
DOE OSTI2021

LncRNA embryonic stem cells expressed 1 (Lncenc1) is identified as a novel regulator in neuropathic pain by interacting with EZH2 and downregulating the expression of Bai1 in mouse microglia

LncRNA embryonic stem cells expressed 1 (Lncenc1), named after its high expression in naïve embryonic stem cells (nESCs), has been rarely studied in almost all pathological processes. Evidences suggest that Lncenc1 is likely to work in the form of RNA-protein complex. Here, we found that Lncenc1 in dorsal root ganglion (DRG) was significantly upregulated in response to mouse nerve injury caused by partial sciatic nerve ligation (pSNL). Overexpression of Lncenc1 mediated by adenoviral expression vector promoted the activation of microglia and the production of inflammatory cytokines including TNF-α, IL-1β and MCP-1. In contrast, knockdown of Lncenc1 suppressed activation of microglia and production of inflammatory cytokines. In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). Either inhibition of EZH2 or overexpression of BAI1 could reverse the effects of Lncenc1 overexpression on microglial activation and neuroinflammation. Finally, the Lncenc1-siRNA was intrathecally injected into pSNL mice, and its effects on neuropathic pain were evaluated. Knockdown of Lncenc1 attenuated the development and maintenance of mechanical and thermal hyperalgesia of pSNL mice, accompanied by an increase in BAI1 expression and decrease in inflammatory cytokines. In conclusion, Lncenc1 contributes to neuropathic pain by interacting with EZH2 and downregulating the BAI1 gene in mouse microglia.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Fractionated Low-Dose Radiation Induces Long-Lasting Inflammatory Responses in the Hippocampal Stem Cell Niche

Despite major technical advances in hippocampus-sparing radiation therapy, radiation-induced injury to the neural stem cell compartment may affect neurocognitive functions. In the brain, glial cells modulate neuronal functions and are major mediators of neuroinflammation. In a preclinical mouse model with fractionated low-dose radiation (LDR), the complex response to radiation-induced injury was analyzed in the hippocampal stem cell compartment over a period of 6 months.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2003

Integrated Electrode Arrays for Neuro-Prosthetic Implants

Arrays of electrodes integrated with chip-scale packages and silicon-based integrated circuits have been proposed for use as medical electronic implants, including neuro-prosthetic devices that might be implanted in brains of patients who suffer from strokes, spinal-cord injuries, or amyotrophic lateral sclerosis. The electrodes of such a device would pick up signals from neurons in the cerebral cortex, and the integrated circuit would perform acquisition and preprocessing of signal data. The output of the integrated circuit could be used to generate, for example, commands for a robotic arm. Electrode arrays capable of acquiring electrical signals from neurons already exist, but heretofore, there has been no convenient means to integrate these arrays with integrated-circuit chips. Such integration is needed in order to eliminate the need for the extensive cabling now used to pass neural signals to data-acquisition and -processing equipment outside the body. The proposed integration would enable progress toward neuro-prostheses that would be less restrictive of patients mobility. An array of electrodes would comprise a set of thin wires of suitable length and composition protruding from and supported by a fine-pitch micro-ball grid array or chip-scale package (see figure). The associated integrated circuit would be mounted on the package face opposite the probe face, using the solder bumps (the balls of the ball grid array) to make the electrical connections between the probes and the input terminals of the integrated circuit. The key innovation is the insertion of probe wires of the appropriate length and material into the solder bumps through a reflow process, thereby fixing the probes in place and electrically connecting them with the integrated circuit. The probes could be tailored to any distribution of lengths and made of any suitable metal that could be drawn into fine wires. Furthermore, the wires could be coated with an insulating layer using anodization or other processes, to achieve the correct electrical impedance. The probe wires and the packaging materials must be biocompatible using such materials as lead-free solders. For protection, the chip and package can be coated with parylene.

Brandon, Erik↗
NASA NTRS1997

Cortical neuronal cytoskeletal changes associated with FIV infection

HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

Non-NASA Center↗
NASA NTRSDate not supplied

A Multi Targeted Dietary Supplement as a Potential Countermeasure for Prolonged, Deep Space Exploration

Deep space exploration, particularly to the Moon and Mars, are currently major goals of NASA and other international space agencies. Long-term space flight presents unique challenges to the human physiology from microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

radiation↗