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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 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

An engineered lactate oxidase based electrochemical sensor for continuous detection of biomarker lactic acid in human sweat and serum

Lactate levels in humans reveal intensity and duration of exertion and provide a critical readout for the severity of life-threatening illnesses such as pediatric sepsis. Using the lactate oxidase enzyme (Lox) from Aerococcus viridians, we demonstrated its functionality for lactate electrochemical sensing in physiological fluids in a lab setting. The structure and dynamics of LOx were validated by crystallography, X-ray scattering, and hydroxyl radical protein footprinting. This provided a validated protein template for understanding and designing an enzyme-based electrochemical sensing elements. Using this template, LOx enzyme variants were generated and compared. Comparison of the variants demonstrates that one exhibits effective lactate sensing at significantly reduced operating voltages. Additionally, we demonstrate that the four hexahistidine-tags on each enzyme tetramer are sufficient for immobilization to create a durable, functional sensor, with no need for a covalent attachment, enabling self-immobilization and eliminating the need for additional immobilization steps. The functionality of the LOx enzyme variants was verified at physiological lactate concentrations in both human serum (0–4 mM) and artificial sweat (0–100 mM) using 3-electrode setups for analysis of the three variants in parallel. Accuracy of measurement in both artificial sweat and human serum were high. Employing a microfluidic flow cell, we successfully monitored varying lactate levels in physiological fluids continuously over a 2h period. Overall, this optimized LOx enzyme, which self-immobilizes onto gold sensing electrodes, facilitates efficient and reliable lactate detection and continuous monitoring at reduced operating voltages suitable for further development towards commercial use.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Serum MicroRNAs as Xerostomia Biomarkers in Patients With Oropharyngeal Cancer Undergoing Radiation Therapy

Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation

Abnormal tau inclusions are hallmarks of Alzheimer's disease and predictors of clinical decline. Several tau PET tracers are available for neurodegenerative disease research, opening avenues for molecular diagnosis in vivo. However, few have been approved for clinical use. Understanding the neurobiological basis of PET signal validation remains problematic because it requires a large-scale, voxel-to-voxel correlation between PET and (immuno) histological signals. Large dimensionality of whole human brains, tissue deformation impacting co-registration, and computing requirements to process terabytes of information preclude proper validation. We developed a computational pipeline to identify and segment particles of interest in billion-pixel digital pathology images to generate quantitative, 3D density maps. The proposed convolutional neural network for immunohistochemistry samples, IHCNet, is at the pipeline's core. We have successfully processed and immunostained over 500 slides from two whole human brains with three phospho-tau antibodies (AT100, AT8, and MC1), spanning several terabytes of images. Our artificial neural network estimated tau inclusion from brain images, which performs with ROC AUC of 0.87, 0.85, and 0.91 for AT100, AT8, and MC1, respectively. Introspection studies further assessed the ability of our trained model to learn tau-related features. We present an end-to-end pipeline to create terabytes-large 3D tau inclusion density maps co-registered to MRI as a means to facilitate validation of PET tracers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

The engineered single guide RNA structure as a biomarker for gene-editing reagent exposure

Abstract CRISPR arrays and CRISPR-associated (Cas) proteins comprise a prevalent adaptive immune system in bacteria and archaea. These systems defend against exogenous parasitic mobile genetic elements. The adaption of single effector CRISPR-Cas systems has massively facilitated gene-editing due to the reprogrammable guide RNA. The guide RNA affords little priming space for conventional PCR-based nucleic acid tests without foreknowledge of the spacer sequence. Further impeding detection of gene-editor exposure, these systems are derived from human microflora and pathogens ( Staphylococcus pyogenes , Streptococcus aureus , etc.) that contaminate human patient samples. The single guide RNA—formed from the CRISPR RNA (crRNA) and transactivating RNA (tracrRNA)—harbors a variable tetraloop sequence between the two RNA segments, complicating PCR assays. Identical single effector Cas proteins are used for gene-editing and naturally by bacteria. Antibodies raised against these Cas proteins are unable to distinguish CRISPR-Cas gene-editors from bacterial contaminant. To overcome the high potential for false positives, we have developed a DNA displacement assay to specifically detect gene-editors. We leveraged the single guide RNA structure as an engineered moiety for gene-editor exposure that does not cross-react with bacterial CRISPRs. Our assay has been validated for five common CRISPR systems and functions in complex sample matrices.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Carotenoid biomarkers in Namibian shelf sediments: Anoxygenic photosynthesis during sulfide eruptions in the Benguela Upwelling System

Significance Anoxygenic photosynthesis by phototrophic sulfur bacteria is prevalent in microbial mat ecosystems and in restricted, highly stratified aquatic environments. This limited distribution reflects their simultaneous requirements for an anoxic habitat, reduced sulfur to supply electrons for carbon fixation, and an appropriate light regime. Although these conditions were often satisfied in ancient seas, as shown by the distinctive carotenoid and chlorophyll pigments preserved in geological samples going back as far as 1.65 billion y, we can find no record of these organisms growing in today’s generally well-ventilated oceans. An array of carotenoids in sediments from the Namibian shelf suggests that green sulfur bacteria, despite their sensitivity to oxygen, can proliferate during episodic toxic gas eruptions in the Benguela Upwelling System.

Ma, Jian↗
DOE OSTI2021

Pharmacokinetics, Metabolite Measurement, and Biomarker Identification of Dermal Exposure to Permethrin Using Accelerator Mass Spectrometry

Impregnating military uniforms and outdoor clothing with the insecticide permethrin is an approach to reduce exposure to insect borne diseases and to repel pests and disease vectors such as mosquitos and sandflies, but the practice exposes wearers to prolonged dermal exposure to the pesticide. Key metabolite(s) from a low dose dermal exposure of permethrin were identified using accelerator mass spectrometry. Metabolite standards were synthesized and a high performance liquide chromatography (HPLC) elution protocol to separate individual metabolites in urine was developed. Six human subjects were exposed dermally on the forearm to 25 mg of permethrin containing 1.0 µCi of 14 C for 8 h. Blood, saliva and urine samples were taken for 7d. Absorption/elimination rates and metabolite concentrations varied by individual. Average absorption was 0.2% of the dose. Serum concentrations rose until 12–24 h postdermal application then rapidly declined reaching predose levels by 72 h. Maximum saliva excretion occurred 6 h postdosing. The maximum urinary excretion rate occurred during 12–24 h; average elimination half-life was 56 h. 3-Phenoxybenzyl alcohol glucuronide was the most abundant metabolite identified when analyzing elution fractions, but most of the radioactivity was in still more polar fractions suggesting extensive degradative metabolism and for which there were no standards. Finally, analyses of archived urine samples with the ultra performance liquid chromatography-accelerator mass spectrometry-mass spectrometry (UPLC-AMS-MS) system isolated a distinct polar metabolite but it was much diminished from the previous analyses a decade earlier.

59 BASIC BIOLOGICAL SCIENCES↗