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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 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Ciliary localization of a light-activated neuronal GPCR shapes behavior

Many neurons in the central nervous system produce a single primary cilium that serves as a specialized signaling organelle. Several neuromodulatory G-protein-coupled receptors (GPCRs) localize to primary cilia in neurons, although it is not understood how GPCR signaling from the cilium impacts circuit function and behavior. We find that the vertebrate ancient long opsin A (VALopA), a Gi-coupled GPCR extraretinal opsin, targets to cilia of zebrafish spinal neurons. In the developing 1-d-old zebrafish, brief light activation of VALopA in neurons of the central pattern generator circuit for locomotion leads to sustained inhibition of coiling, the earliest form of locomotion. We find that a related extraretinal opsin, VALopB, is also Gi-coupled, but is not targeted to cilia. Light-induced activation of VALopB also suppresses coiling, but with faster kinetics. We identify the ciliary targeting domains of VALopA. Retargeting of both opsins shows that the locomotory response is prolonged and amplified when signaling occurs in the cilium. We propose that ciliary localization provides a mechanism for enhancing GPCR signaling in central neurons.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Current Status of Radiopharmaceutical Therapy

In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of {sup 131}I, treatment of liver cancer with {sup 90}Y microspheres, the treatment of bony metastases with {sup 223}Ra, and the treatment of neuroendocrine tumors with {sup 177}Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient’s body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS1992

Millimeter and hard x ray/gamma ray observations of solar flares during the June 1991 GRO campaign

We have carried out high-spatial-resolution millimeter observations of solar flares using the Berkeley-Illinois-Maryland Array (BIMA). At the present time, BIMA consists of only three elements, which is not adequate for mapping highly variable solar phenomena, but is excellent for studies of the temporal structure of flares at millimeter wavelengths at several different spatial scales. We present BIMA observations made during the Gamma Ray Observatories (GRO)/Solar Max 1991 campaign in Jun. 1991 when solar activity was unusually high. Our observations covered the period 8-9 Jun. 1991; this period overlapped the period 4-15 Jun. when the Compton Telescope made the Sun a target of opportunity because of the high level of solar activity.

Kundu, M. R.↗
NASA NTRS1986

The use of active microwave sensors in search and rescue operations

The possibility of utilizing low-orbit active microwave sensors in Search and Rescue (SAR) operations to detect and positionally locate scenes of distress is studied. The use of a scanning type system, i.e., rotating a highly directional antenna as opposed to more complex synthetic aperture type system is addressed. Targets for this system will be passive reflectors, not active transmitters like EPIRBs; reflectors which could be easily stowed, require little to no maintenance, could be quickly erected and can be more affordable than battery powered alternatives. Presented are parametric analyses to determine the required antenna gains and reflector areas for various frequencies and orbit altitudes. Also, major issues are raised as well as indicating areas requiring further study.

Tillotson, Tom↗
DOE OSTI2022

Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types

Cellular senescence is a driver of many age-related pathologies. There is an active search for pharmaceuticals termed senolytics that can mitigate or remove senescent cells in vivo by targeting genes that promote the survival of senescent cells. We utilized single-cell RNA sequencing to identify CRYAB as a robust senescence-induced gene and potential target for senolysis. Using chemical inhibitor screening for CRYAB disruption, we identified 25-hydroxycholesterol (25HC), an endogenous metabolite of cholesterol biosynthesis, as a potent senolytic. We then validated 25HC as a senolytic in mouse and human cells in culture and in vivo in mouse skeletal muscle. Thus, 25HC represents a potential class of senolytics, which may be useful in combating diseases or physiologies in which cellular senescence is a key driver.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation

The class IB phosphoinositide 3-kinase (PI3K), PI3Kγ, is a master regulator of immune cell function and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kγ function is the association of the p110γ catalytic subunit to either a p101 or p84 regulatory subunit, which mediates activation by G protein–coupled receptors. Here, we report the cryo–electron microscopy structure of a heterodimeric PI3Kγ complex, p110γ-p101. This structure reveals a unique assembly of catalytic and regulatory subunits that is distinct from other class I PI3K complexes. p101 mediates activation through its Gβγ-binding domain, recruiting the heterodimer to the membrane and allowing for engagement of a secondary Gβγ-binding site in p110γ. Mutations at the p110γ-p101 and p110γ–adaptor binding domain interfaces enhanced Gβγ activation. A nanobody that specifically binds to the p101-Gβγ interface blocks activation, providing a novel tool to study and target p110γ-p101–specific signaling events in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Self-Supervised Anomaly Detection via Neural Autoregressive Flows with Active Learning

Many self-supervised methods have been proposed with the target of image anomaly detection. These methods often rely on the paradigm of data augmentation with predefined transformations such as flipping, cropping, and rotations. However, it is not straightforward to apply these techniques for non-image data, such as time series or tabular data, while the performance of the existing deep approaches has been under our expectation on tasks beyond images. In this work, we propose a novel active learning (AL) scheme that relied on neural autoregressive flows (NAF) for self-supervised anomaly detection, specifically on small-scale data. Unlike other generative models such as GANs or VAEs, flow-based models allow to explicitly learn the probability density and thus can assign accurate likelihoods to normal data which makes it usable to detect anomalies. The proposed NAF-AL method is achieved by efficiently generating random samples from latent space and transforming them into feature space along with likelihoods via invertible mapping. The samples with lower likelihoods are selected and further checked by outlier detection using Mahalanobis distance. The augmented samples incorporating with normal samples are used for training a better detector so as to approach decision boundaries. Compared with random transformations, NAF-AL can be interpreted as a likelihood-oriented data augmentation that is more efficient and robust. Extensive experiments show that our approach outperforms existing baselines on multiple time series and tabular datasets, and a real-world application in advanced manufacturing, with significant improvement on anomaly detection accuracy and robustness over the state-of-the-art.

Zhang, Jiaxin↗
NASA NTRS1993

The star identification, pointing and tracking system of UVSTAR, an attached payload instrument system for the Shuttle Hitchhiker-M platform

We describe an algorithm for star identification and pointing/tracking of a spaceborne electro-optical system and simulation analyses to test the algorithm. The algorithm will be implemented in the guiding system of UVSTAR, a spectrographic telescope for observations of astronomical and planetary sources operating in the 500-1250 A waveband at approximately 1 A resolution. The experiment is an attached payload and will fly as a Hitchhiker-M payload on the Shuttle. UVSTAR includes capabilities for independent target acquisition and tracking. The spectrograph package has internal gimbals that allow angular movement of plus or minus 3 deg from the central position. Rotation about the azimuth axis (parallel to the Shuttle z axis) and elevation axis (parallel to the Shuttle x axis) will actively position the field of view to center the target of interest in the fields of the spectrographs. The algorithm is based on an on-board catalog of stars. To identify star fields, the algorithm compares the positions of stars recorded by the guiding imager to positions computed from the on-board catalog. When the field has been identified, its position within the guiding imager field of view can be used to compute the pointing corrections necessary to point to a target of interest. In tracking mode, the software uses the past history to predict the quasi-periodic attitude control motions of the shuttle and sends pointing commands to cancel the motion and stabilize UVSTAR on the target. The guiding imager (guider) will have an 80-mm focal length and f/1.4 optics giving a field of view of 6 deg x 4.5 deg using a 385 x 288 pixel intensified CCD. It will be capable of providing high accuracy (better than 2 arc-sec) attitude determination from coarse (6 deg x 4.5 deg) initial knowledge of the pointing direction; and of pointing toward the target. It will also be capable of tracking at the same high accuracy with a processing time of less than a few hundredths of a second.

Decarlo, Francesco↗
NASA NTRS2000

Fuzzy Behavior Modulation with Threshold Activation for Autonomous Vehicle Navigation

This paper describes fuzzy logic techniques used in a hierarchical behavior-based architecture for robot navigation. An architectural feature for threshold activation of fuzzy-behaviors is emphasized, which is potentially useful for tuning navigation performance in real world applications. The target application is autonomous local navigation of a small planetary rover. Threshold activation of low-level navigation behaviors is the primary focus. A preliminary assessment of its impact on local navigation performance is provided based on computer simulations.

Tunstel, Edward↗
NASA NTRSDate not supplied

NASA Environmental Control and Life Support Technology Development for Exploration: 2021 to 2022 Overview

Over the past year, significant progress has occurred in technology development, ground testing, and ISS technology demonstrations within the NASA Environmental Control and Life Support (ECLSS) community. This paper provides a technology development update in the following capability areas: life support, environmental monitoring, fire safety, and logistics. Technologies for exploration missions must be reliable in their operation which support crewed mission phases. However, they also need to be put into a reduced use or dormant states to support uncrewed mission phases and then successfully and reliably returned to a nominal state to support crew. Multi-year demonstration of systems operation across this range of conditions are essential to mission success. Project overviews will include how the current activity supports the goal of multi-year demonstrations, planned follow-on activities, and what type of exploration mission elements are targeted for infusion. Technologies must be demonstrated and validated early enough to inform early exploration element milestone reviews (mission concept reviews, systems requirement reviews and no later than preliminary design reviews) so that supporting vehicle systems can also be matured. Consequently, for low technology readiness activities, it is important to also identify which mission elements they might infuse into and how they may offer potential operational, dormancy, or mass benefits. While low TRL technology timelines may not support initial mission needs, early infusion is still reasonable with sufficient testing to validate performance and reliability.

Life Support↗
DOE OSTI2023

Biochemical Process Modeling and Simulation (BPMS)

The Biochemical Process Modeling and Simulation project aims to reduce the cost and time of research by applying theory, modeling, and simulation to the most relevant bottlenecks in the biochemical process. We use molecular modeling, quantum mechanics, metabolic modeling, fluid dynamics, and reaction-diffusion methods in close collaboration with pretreatment, hydrolysis, upgrading, and TEA. The project's outcomes are increased yields and efficiency of the biochemical process, added value to products, and reduced price of fuels by specifically targeting catalytic efficiency, reactor design, enzyme efficiency, and microbial design. We work closely with experimental projects to identify problems and iterate with experiments to find and refine solutions. By working with experimentalists, we decide on problems that can be solved with simulation that could otherwise not be solved or would take too long with experiment alone to reach BETO's targets. Over the years, we have produced solutions that have resulted in determining the most likely fatty-acid derivative for passive transport out of bacteria that upgrade biomass, and we have also designed enzyme mutations for enhanced lignin upgrading. Metabolic models have been developed to tune the activity of 2,3 butanediol production for the 2030 target. A computational method to deliver understanding of how complex omics data can be interpreted in the metabolic pathways of organisms used in the Agile Biofoundry. We have found methods to overcome specific barriers and continue to develop those methods. Our reactor studies have guided the design of both the microbes and reactors for aerobic and micro-aerobic production at all scales and have been instrumental in improving the accuracy of techno-economic analysis models. This project is essential in the process of selecting the final processes for 2030 SAF production targets. More specifically, recently, we have: 1) Predicted the strength of the basic structural interactions in commodity plastics to provide guidance for plastics upcycling strategies. 2) Developed computational tool to improve the characterization of lignin-derived compounds 3) Developed new methodologies to enable Machine Learning-based Directed Evolution for protein engineering. 4) Developed Machine Learning methods to predict protein promiscuity and mutations to further improve microbial and enzymatic driven processes and demonstrated the utility of ML approaches to engineering proteins from sparse experimental datasets. 5) Developed new methods to enable high-fidelity simulation of aerobic fermentation at industrial scale and resolving mismatch of time scales through subcycling/operator splitting 7) Identified the difficulty in preventing local high-oxygen conditions in industrial bubble columns, which leads to less-desirable acetoin production, suggesting future research directions in alternative reactor configurations (e.g loop reactors, shallow-channel reactors).

BIOMASS FUELS↗
DOE OSTI2020

Discovery of a Natural Product That Binds to the Mycobacterium tuberculosis Protein Rv1466 Using Native Mass Spectrometry

Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound’s cellular activity. A fraction derived from the plant Polyalthia sp. showed activity against Mycobacterium tuberculosis at 62.5 μge/μL. A known compound, altholactone, was identified from this fraction that showed activity towards M. tuberculosis at an minimum inhibitory concentration (MIC) of 64 μM. Retrospective analysis of a target-based screen against a TB proteome panel using native mass spectrometry established that the active fraction was bound to the mycobacterial protein Rv1466 with an estimated pseudo-Kd of 42.0 ± 6.1 µM. Our findings established Rv1466 as the potential molecular target of altholactone, which is responsible for the observed in vivo toxicity towards M. tuberculosis .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Identification of 2-Hydroxyacyl-CoA Synthases with High Acyloin Condensation Activity for Orthogonal One-Carbon Bioconversion

One-carbon (C1) compounds are emerging as cost-effective and potentially carbon-negative feedstocks for biomanufacturing, which require efficient, versatile metabolic platforms for the synthesis of value-added products. Synthetic formyl-CoA elongation (FORCE) pathways allow diverse product synthesis from C1 compounds via iterative C1 elongation, operating independently from the host metabolism with reduced engineering complexity and improved theoretical yields. However, a major bottleneck was identified as the suboptimal kinetics of the core C1–C1 condensation enzyme, 2-hydroxyacyl-CoA synthase (HACS), catalyzing the acyloin condensation reaction between formaldehyde and formyl-CoA. Furthermore, we used a combinatorial approach of bioprospecting and rational protein engineering to identify multiple HACS variants with significantly improved activities toward C1 substrates. Sequence and structure alignment of the active variants elucidated the key regions for the catalytic function, which were targeted for mutagenesis, leading to improved catalytic efficiency. In parallel, a consecutive round of bioprospecting for homologs with high similarity with active variants revealed a highly active HACS variant exhibiting up to 7-fold improvement in catalytic efficiency (k cat /K M ) and 14-fold improvement in the FORCE pathway flux in vivo compared to the previous reports. Upon further optimization of the downstream pathway, the orthogonal C1-to-product bioconversion system showed a metabolic flux of up to 700 μM glycolate OD –1 h –1 (2.1 mmol gDCW –1 h –1 ) and an industrially relevant glycolate titer, rate, and yield of 5.2 g L –1 (67.8 mM), 0.22 g L –1 h –1 , and 94% carbon yield, respectively.

2-hydroxyacyl-CoA synthase↗
DOE OSTI2025

Radioisotope production at the Spallation Neutron Source: Design concept of isotope production target

Upon completion of the Second Target Station (STS) Project in the mid 2030s, the Spallation Neutron Source accelerator at Oak Ridge National Laboratory will deliver a 2.7 MW proton beam to the neutron production targets. In the post-STS phase, the accelerator will have a reserve beam power capacity of at least 100 kW beyond what the two neutron production targets will receive, which could potentially be ramped up to 300 kW. In this paper, a design concept for a radioisotope production target that could utilize 250 kW of the reserve beam power capacity is presented. The target consists of thorium discs encapsulated in 316L austenitic steel shells that are cooled by water. The estimated post-irradiation activity of Ac-225 and Ra-225, critical medical radioisotopes used in targeted alpha therapy cancer treatment, is calculated at the end of bombardment after a 14 day long irradiation time. Thermal and structural analyses are performed on the basis of calculated nuclear heating data. The technical feasibility of a high-power target under a 250-kW beam load with an extremely low duty factor of $3.5\cdot 10^{-6}$ is presented from thermal, structural and fatigue lifetime perspectives.

Lee, Yong Joong [ORNL] (ORCID:0000000298381723)↗
NASA NTRS1986

VEGA Pathfinder navigation for Giotto Halley encounter

Results of the VEGA Pathfinder concept which was used to successfully target the European Space Agnecy's Giotto spacecraft to a 600 km encounter with the comet Halley are presented. Pathfinder was an international cooperative navigation activity involving USSR, European and U.S. space agencies. The final Giotto targeting maneuver was based on a comet location determined from optical data acquired by the earlier arriving Soviet VEGA spacecraft. Inertial pointing angles extracted from optical images of the comet nucleus were combined with a precise estimate of the VEGA encounter orbits determined using VLBI data acquired by NASA's Deep Space Network to predict the location of Halley at Giotto encounter. This article describes the VLBI techniques used to determine the VEGA orbits and shows that the insensitivity of the VLBI data strategy to unmodeled dynamic error sources resulted in estimates of the VEGA orbits with an accuracy of 50 km.

Ellis, J.↗
NASA NTRS1986

VEGA Pathfinder navigation for Giotto Halley encounter - An application of VLBI techniques

Results of the VEGA Pathfinder concept which was used to successfully target the European Space Agency's Giotto spacecraft to a 600 km encounter with the comet Halley are presented. Pathfinder was an international cooperative navigation activity involving USSR, European and U.S. space agencies. The final Giotto targeting maneuver was based on a comet location determined from optical data acquired by the earlier arriving Soviet VEGA spacecraft. Inertial pointing angles extracted from optical images of the comet nucleus were combined with a precise estimate of the VEGA encounter orbits determined using VLBI data acquired by NASA's Deep Space Network to predict the location of Halley at Giotto encounter. This article describes the VLBI techniques used to determine the VEGA orbits and shows that the insensitivity of the VLBI data strategy to unmodeled dynamic error sources resulted in estimates of the VEGA orbits with an accuracy of 50 km.

Ellis, Jordan↗
DOE OSTI2021

Targeted polyelectrolyte complex micelles treat vascular complications in vivo

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92a EC-TG /Apoe –/– ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe –/– mice. We tested the therapeutic effectiveness of the VCAM-1–targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1–targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti–miR-92a therapy in treating atherosclerosis and stenosis in Apoe –/– mice is markedly enhanced by the VCAM-1–targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Developing a Peptide That Inhibits DNA Repair by Blocking the Binding of Artemis and DNA Ligase IV to Enhance Tumor Radiosensitivity

Artemis and DNA Ligase IV are 2 critical elements in the nonhomologous end joining pathway of DNA repair, acting as the nuclease and DNA ligase, respectively. Enhanced cellular radiosensitivity by inhibition of either protein contributes to a promising approach to develop molecular targeted radiosensitizers. The interaction between Artemis and DNA Ligase IV is required for the activation of Artemis as nuclease at 3’overhang DNA; thus, we aim to generate an inhibitory peptide targeting the interaction between Artemis and DNA Ligase IV for novel radiosensitizer development.

62 RADIOLOGY AND NUCLEAR MEDICINE↗