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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 469 records · Page 26
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Graphene K‐Tape Meshes for Densely Distributed Human Motion Monitoring

Abstract Wearable sensors that measure parameters associated with physical activity and bodily motions have been regarded as an indispensable tool for assessing personal wellness. Recent advances in nanocomposite strain sensors have been successfully used for monitoring skin strains and other strain‐derived physiological parameters. This study complements the existing body of work and presents a flexible, self‐adhering, fabric‐based wearable sensor for measuring skin strains and human motions. Graphene nanosheet thin films are directly spray‐coated onto kinesiology tape (K‐Tape) to obtain a self‐adhering strain sensor of high sensitivity and linearity. Their stable sensing performance and high repeatability are verified, while human subject tests confirm that they adequately capture muscle engagement during functional movements. In addition, densely distributed strain monitoring can be achieved using an electrical impedance tomography measurement approach and algorithm. Spatial strain sensing is successfully demonstrated using a single strip of piezoresistive K‐Tape, as well as when a K‐Tape network or mesh pattern is formed. The results show promise for using graphene K‐Tape meshes to measure how specific major muscle groups engage during different physical activities.

Lin, Yun‐An↗
DOE OSTI2020

Activity–Based Protein Profiling of Bile Salt Hydrolysis in the Human Gut Microbiome with Beta–Lactam or Acrylamide–Based Probes

Microbial bile salt hydrolases (BSHs) found in the intestine catalyze the deconjugation of taurine– and glycine–linked bile salts produced in the liver. The resulting bile salts are biological detergents and are critical in aiding lipophilic nutrient digestion. Therefore, the activity of BSHs in the gut microbiome is directly linked to human metabolism and overall health. Bile salt metabolism has also been associated with disease phenotypes such as liver and colorectal cancer. In order to reshape the gut microbiome to optimize bile salt metabolism, tools to characterize and quantify these processes must exist to enable a much–improved understanding of how metabolism goes awry in the face of disease, and how it can be improved through an altered lifestyle and environment. Furthermore, it is necessary to attribute metabolic activity to specific members and BSHs within the microbiome. To this end, we have developed activity–based probes with two different reactive groups to target bile salt hydrolases. Finally, these probes bind similarly to the authentic bile salt substrates, and we demonstrate enzyme labeling of active bile salt hydrolases by using purified protein, cell lysates, and in human stool.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Connectivity‐based parcellation of normal and anatomically distorted human cerebral cortex

Abstract For over a century, neuroscientists have been working toward parcellating the human cortex into distinct neurobiological regions. Modern technologies offer many parcellation methods for healthy cortices acquired through magnetic resonance imaging. However, these methods are suboptimal for personalized neurosurgical application given that pathology and resection distort the cerebrum. We sought to overcome this problem by developing a novel connectivity‐based parcellation approach that can be applied at the single‐subject level. Utilizing normative diffusion data, we first developed a machine‐learning (ML) classifier to learn the typical structural connectivity patterns of healthy subjects. Specifically, the Glasser HCP atlas was utilized as a prior to calculate the streamline connectivity between each voxel and each parcel of the atlas. Using the resultant feature vector, we determined the parcel identity of each voxel in neurosurgical patients ( n = 40) and thereby iteratively adjusted the prior. This approach enabled us to create patient‐specific maps independent of brain shape and pathological distortion. The supervised ML classifier re‐parcellated an average of 2.65% of cortical voxels across a healthy dataset ( n = 178) and an average of 5.5% in neurosurgical patients. Our patient dataset consisted of subjects with supratentorial infiltrating gliomas operated on by the senior author who then assessed the validity and practical utility of the re‐parcellated diffusion data. We demonstrate a rapid and effective ML parcellation approach to parcellation of the human cortex during anatomical distortion. Our approach overcomes limitations of indiscriminately applying atlas‐based registration from healthy subjects by employing a voxel‐wise connectivity approach based on individual data.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A missense variant remote from the active site impairs stability of human phosphoglucomutase 1

Abstract Missense variants of human phosphoglucomutase 1 (PGM1) cause the inherited metabolic disease known as PGM1 deficiency. This condition is categorised as both a glycogen storage disease and a congenital disorder of glycosylation. Approximately 20 missense variants of PGM1 are linked to PGM1 deficiency, and biochemical studies have suggested that they fall into two general categories: those affecting the active site and catalytic efficiency, and those that appear to impair protein folding and/or stability. In this study, we characterise a novel variant of Arg422, a residue distal from the active site of PGM1 and the site of a previously identified disease‐related variant (Arg422Trp). In prior studies, the R422W variant was found to produce insoluble protein in a recombinant expression system, precluding further in vitro characterisation. Here we investigate an alternative variant of this residue, Arg422Gln, which is amenable to experimental characterisation presumably due to its more conservative physicochemical substitution. Biochemical, crystallographic, and computational studies of R422Q establish that this variant causes only minor changes in catalytic efficiency and 3D structure, but is nonetheless dramatically reduced in stability. Unexpectedly, binding of a substrate analog is found to further destabilise the protein, in contrast to its stabilising effect on wild‐type PGM1 and several other missense variants. This work establishes Arg422 as a lynchpin residue for the stability of PGM1 and supports the impairment of protein stability as a pathomechanism for variants that cause PGM1 deficiency. Synopsis Biochemical and structural studies of a missense variant far from the active site of human PGM1 identify a residue with a key role in enzyme stability.

Stiers, Kyle M.↗
DOE OSTI2025

Characterization of Cytokine Treatment on Human Pancreatic Islets by Top‐Down Proteomics

Type 1 diabetes (T1D) results from autoimmune-mediated destruction of insulin-producing β cells in the pancreatic islet. This process is modulated by pro-inflammatory cytokine signaling, which has been previously shown to alter protein expression in ex vivo islets. Herein, we applied top-down proteomics to globally evaluate proteoforms from human islets treated with proinflammatory cytokines (interferon-γ and interleukin-1β). We measured 1636 unique proteoforms across six donors and two time points (control and 24 h post-treatment) and observed consistent changes in abundance across the glicentin-related pancreatic polypeptide (GRPP) and major proglucagon fragment regions of glucagon, as well as the LF-19/catestatin and vasostatin-1/2 region of chromogranin-A. We also observe several proteoforms that increase after cytokine-treatment or are exclusively observed after cytokine-treatment, including forms of beta-2 microglobulin (B2M), high-mobility group N2 protein (HMGN2), and chemokine (C-X-C motif) ligands (CXCL). Together, our quantitative results provide a baseline proteoform profile for human islets and identify several proteoforms that may serve as interesting candidate markers for T1D progression or therapeutic intervention.

glucagon↗
DOE OSTI2025

The structural basis for the broad aldehyde specificity of the aminoaldehyde dehydrogenase PauC from the human pathogen Pseudomonas aeruginosa

Abstract Despite significant differences in size and formal charge, the aldehyde dehydrogenasePaPauC (PA5312) fromPseudomonas aeruginosaPAO1 efficiently catalyzes the NAD + ‐dependent oxidation of the aminoaldehydes formed in polyamines degradation. We report here thatPaPauC also oxidizes 4‐guanidinebutyraldehyde, formed in one arginine degradation pathway, trimethylaminobutyraldehyde, of unknown metabolic origin, and indole‐3‐acetaldehyde, a precursor of the plant growth‐promoting hormone indoleacetic acid.PaPauC has been proposed as a potential target for combatingP. aeruginosa. However, understanding its structure–function relationships, crucial for developing specific inhibitors, is lacking. Using X‐ray crystallography, we identified the structural characteristics that determinePaPauC broad aldehyde specificity: a spacious aldehyde‐entrance tunnel and six active‐site residues. Docking simulations, site‐directed mutagenesis, and kinetic analyses support the interactions of Lys479 with glutamylated aminoaldehydes; Phe169, Trp176, and Phe467 with amino and guanidinium groups through cation–π interactions and with the indole group via NH–π and CH–π interactions; Asp459 with amino and indole groups; and Thr303 with amide and guanidinium groups. Exploiting the distinctive structural features of thePaPauC active site could aid in developing specific inhibitors to combatP. aeruginosainfections in humans and animals, as well as in preventing its colonization of plants, which are abundantP. aeruginosareservoirs and, therefore, a significant source of human infections.

Biochemistry & Molecular Biology↗
DOE OSTI2022

Structural and functional analysis of the human cone‐rod homeobox transcription factor

Abstract The cone‐rod homeobox (CRX) protein is a critical K50 homeodomain transcription factor responsible for the differentiation and maintenance of photoreceptor neurons in the vertebrate retina. Mutant alleles in the human gene encoding CRX result in a variety of distinct blinding retinopathies, including retinitis pigmentosa, cone‐rod dystrophy, and Leber congenital amaurosis. Despite the success of using in vitro biochemistry, animal models, and genomics approaches to study this clinically relevant transcription factor over the past 25 years since its initial characterization, there are no high‐resolution structures in the published literature for the CRX protein. In this study, we use bioinformatic approaches and small‐angle X‐ray scattering (SAXS) structural analysis to further understand the biochemical complexity of the human CRX homeodomain (CRX‐HD). We find that the CRX‐HD is a compact, globular monomer in solution that can specifically bind functional cis‐regulatory elements encoded upstream of retina‐specific genes. This study presents the first structural analysis of CRX, paving the way for a new approach to studying the biochemistry of this protein and its disease‐causing mutant protein variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Predicting transport of intra-articularly injected growth factor fusion proteins into human knee joint cartilage

There are no drugs or treatment methods known to prevent the development of post-traumatic osteoarthritis (PTOA), a type of osteoarthritis (OA) that is triggered by traumatic joint injuries and accounts for ~12% of the nearly 600 million OA cases worldwide. Lack of effective drug delivery techniques remains a major challenge in developing clinically effective treatments, but cationic delivery carriers can help overcome this challenge. Scaling up treatments that are effective in in vitro models to achieve success in preclinical in vivo models and clinical trials is also a challenging problem in the field. Here we use a cationic green fluorescent protein (GFP) as a carrier to deliver Insulin-Like Growth Factor 1 (IGF-1), a drug considered as a potential therapeutic for PTOA. GFP-IGF-1 conjugates were first synthesized as fusion proteins with different polypeptide linkers, and their transport properties were characterized in human cartilage explants. In vitro experimental data were used to develop a predictive mathematical transport model that was validated using an independent in vitro experimental data set. In this study, the model was used to predict the transport of these fusion proteins upon intra-articular injection into human knee joints. The predictions included results for the rate and extent of fusion protein penetration into cartilage, and the maximum levels of fusion proteins that would escape into systemic circulation through the joint capsule. Together, our transport measurements and model set the stage for translation of such explant culture studies to in vivo preclinical studies and potentially clinical application.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Optimized production of a bioactive human recombinant protein from the microalgae Chlamydomonas reinhardtii grown at high density in a fed-batch bioreactor

Microalgae have been identified as an alternative platform to produce high-quality biomass and subsequent bioproducts, such as foods, feeds, nutritional supplements, recombinant proteins, and biofuels. Traditional biotechnological hosts for therapeutic proteins, such as the bacteria Escherichia coli and mammalian CHO cells, have long been established as the dominate platforms, but recent advances have shown that microalgae can potentially serve as an alternative platform. In the present study, we examine the potential of the microalga Chlamydomonas reinhardtii to produce a complex human recombinant protein in a high-density heterotrophic culture. The recombinant human protein, ICAM-1, was targeted for secretion to the extracellular media of the culture from cells grown in a bioreactor using a fed-batch strategy to achieve high cell density. Ultimately, this resulted in a maximum biomass titer of 40 g/L and a recombinant protein titer of 50 mg/L. The algal-produced ICAM-1 protein showed comparable bioactivity to mammalian cell culture produced ICAM-1, as measured using binding assays for its native ligand LFA-1. This work shows that C. reinhardtii is a viable option to produce complex recombinant proteins, with native biological activity, at high concentrations using a fed batch heterotrophic growth strategy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

2.5 Å-resolution structure of human CDK-activating kinase bound to the clinical inhibitor ICEC0942

The human CDK-activating kinase (CAK), composed of CDK7, cyclin H, and MAT1, is involved in the control of transcription initiation and the cell cycle. Because of these activities, it has been identified as a promising target for cancer chemotherapy. A number of CDK7 inhibitors have entered clinical trials, among them ICEC0942 (also known as CT7001). Structural information can aid in improving the affinity and specificity of such drugs or drug candidates, reducing side effects in patients. Here, we have determined the structure of the human CAK in complex with ICEC0942 at 2.5 Å-resolution using cryogenic electron microscopy. Our structure reveals conformational differences of ICEC0942 compared with previous X-ray crystal structures of the CDK2-bound complex, and highlights the critical ability of cryogenic electron microscopy to resolve structures of drug-bound protein complexes without the need to crystalize the protein target.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

helixCAM: A platform for programmable cellular assembly in bacteria and human cells

Interactions between cells are indispensable for signaling and creating structure. The ability to direct precise cell-cell interactions would be powerful for engineering tissues, understanding signaling pathways, and directing immune cell targeting. In humans, intercellular interactions are mediated by cell adhesion molecules (CAMs). However, endogenous CAMs are natively expressed by many cells and tend to have cross-reactivity, making them unsuitable for programming specific interactions. Here, we showcase “helixCAM,” a platform for engineering synthetic CAMs by presenting coiled-coil peptides on the cell surface. helixCAMs were able to create specific cell-cell interactions and direct patterned aggregate formation in bacteria and human cells. Based on coiled-coil interaction principles, we built a set of rationally designed helixCAM libraries, which led to the discovery of additional high-performance helixCAM pairs. Finally, we applied this helixCAM toolkit for various multicellular engineering applications, such as spherical layering, adherent cell targeting, and surface patterning.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Understanding the adsorption and potential tear film stability properties of recombinant human lubricin and bovine submaxillary mucins in an in vitro tear film model

The wetting and adsorption properties for two glycoproteins, recombinant human lubricin and bovine submaxillary mucins (BSM) were evaluated on hydrophilic and hydrophobic glass dome surfaces in a simplified in vitro tear film model. Herein, we show that both recombinant human lubricin (rh-lubricin) and BSM solutions render surfaces hydrophilic and when the fluid films reach 500 nm or less, the fluids resist evaporation-driven breakup through a volumetric flux across the surface, which we believe is due to evaporation-driven solutocapillary flows. rh-Lubricin was able to maintain a wet film without spontaneous breakup for longer periods of time than BSM at lower concentrations, which we attribute to differences in adsorption properties, measured by QCM-D, that result from surface charge and structural differences (confirmed by zeta potential, DLS, and SAXS measurements).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Energy impact of human health and wellness lighting recommendations for office and classroom applications

The goal of this investigation was to evaluate potential energy impacts of circadian lighting design recommendations gaining attention in a variety of common applications such as offices and classrooms. The renewed focus on health along with advances in SSL technology capabilities has underscored that there is still much to learn regarding the relationship between light and human physiology. The energy implications of designing to address these possible physiological effects are not yet fully understood. Beyond the fact that the basic metric of luminous efficacy (lumens per watt) does not cover these other effects, the emerging science seems to indicate that addressing a holistic view of the human needs in most applications may mean a need for increased light and associated energy use by electric lighting systems. Within the two applications considered, lumen output, spectral characteristics, surface reflectance distribution and desk orientation were varied to explore the magnitude of potential effects. Meeting current IES illuminance recommendations did not satisfy existing EML and CS recommendations for any of the simulations. In some cases, satisfying circadian metric recommendations required average illuminance that was more than double IES recommendations, which may negatively impact lighting quality as well. Using results from 45 unique simulation conditions, it was estimated that lighting energy use may increase between 10% and 100% due to increased luminaire light levels used to meet circadian lighting design recommendations listed in current building standards such as WELL v2 Q2 2019, UL Design Guideline 24480, and CHPS Core Criteria 3.0.

circadian lighting, lighting simulation, solid sta↗
DOE OSTI2026

Comparison of automated chemical-guided segmentation and human annotation of soil organic matter in X-ray microcomputed tomography imaging in contrasted soil types

Soil organic matter (OM) formation and persistence is strongly influenced by the spatial distribution of organic substrates and microscale soil heterogeneity by dictating OM accessibility to microorganisms. However, traditional size and/or density fractionation techniques disrupt aggregate architecture, eliminating spatial information needed to fully understand intra-aggregate OM distribution. To quantify three-dimensional OM spatial distribution and automate segmentation in X-ray microcomputed tomography (µCT) imaging without human annotation bias, we developed an iodine gas vapor (I2) based staining workflow that eliminates labor-intensive manual annotation while maintaining segmentation accuracy, using aggregates from four taxonomically diverse soils (Xerofluvent, Haploxeroll Sphagnofibrist, Palehumult) with an 8-fold range of soil organic carbon. Human annotation of 10 µCT slices by the experienced and inexperienced annotators resulted in variations up to 3% in the Dice similarity coefficient (DSC), reflecting a degree of inherent subjectivity of manual labeling. Such inconsistencies are expected to compound as the number of manually annotated slices increases. Dual-energy µCT imaging at 33.1 keV (below the iodine (I) K-edge) and 33.2 keV (above the I K-edge) was used to resolve aggregate microstructure following I2 staining. The automated image subtraction pipeline identified OM regions by the I Kedge induced brightness increases, achieving DSC values of 0.58–0.83 relative to an experienced annotator. Sensitivity analyses revealed that the reconstruction alpha value—optimized via the open-source tool TomocuPy—and the 3D registration slice count were the primary determinants of accuracy, providing a novel benchmark for dual-energy soil imaging. The pipeline without GPU acceleration achieved 9.6 to 43.2 times faster than manual annotation. Using GPU-accelerated image post-processing and affine transformation matrices, the pipeline successfully segmented OM elements for large-scale datasets (3232×3232 pixel, 2048 slices) within ~5200 s from raw file acquisition to segmented output. The high-throughput approach enables the quantification of OM spatial distribution across diverse and heterogeneous soil.

Soil microbial biomass↗
DOE OSTI2021

Ultra-high-dose-rate FLASH and Conventional-Dose-Rate Irradiation Differentially Affect Human Acute Lymphoblastic Leukemia and Normal Hematopoiesis

Ultra-high-dose-rate FLASH radiation therapy has been shown to minimize side effects of irradiation in various organs while keeping antitumor efficacy. This property, called the FLASH effect, has caused enthusiasm in the radiation oncology community because it opens opportunities for safe dose escalation and improved radiation therapy outcome. Here, we investigated the impact of ultra-high-dose-rate FLASH versus conventional-dose-rate (CONV) total body irradiation (TBI) on humanized models of T-cell acute lymphoblastic leukemia (T-ALL) and normal human hematopoiesis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo

Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, in this work, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Asynchronous aging and turnover of human circulating and tissue-resident memory T cells across sites

Memory T cells are maintained in tissues as circulating effector-memory (T EM ) and tissue-resident (T RM ) populations for protective immunity, though the role of site and subset in memory persistence remains undefined. Here, in this work, we investigated age-associated dynamics of human T cells in lymphoid organs, mucosal sites, and blood over 10 decades of life using retrospective radiocarbon ( 14 C) birth dating, along with cellular, transcriptome, and epigenetic profiling. Memory T cells across peripheral sites exhibited continuous turnover with mean lifespans of 1–2 years, while the spleen contained longer-lived T cells. Over age, T EM cells expressed senescent markers and a GZMK transcriptional signature, while T RM cells maintained site-specific resident phenotypes without exhibiting features of senescence. Both T EM and T RM cells showed age-associated DNA hypomethylation, though T RM cells exhibited more epigenetically regulated genes. Together, our findings reveal asynchronous aging of human memory T cells by subset and site, as well as persistence of T RM cells without immunosenescence.

T cells↗
DOE OSTI2021

Patient mutations in human ATP:cob(I)alamin adenosyltransferase differentially affect its catalytic versus chaperone functions

Human ATP:cob(I)alamin adenosyltransferase (ATR) is a mitochondrial enzyme that catalyzes an adenosyl transfer to cob(I)alamin, synthesizing 5'-deoxyadenosylcobalamin (AdoCbl) or coenzyme B 12 . ATR is also a chaperone that escorts AdoCbl, transferring it to methylmalonyl-CoA mutase, which is important in propionate metabolism. Mutations in ATR lead to methylmalonic aciduria type B, an inborn error of B12 metabolism. Our previous studies have furnished insights into how ATR protein dynamics influence redox-linked cobalt coordination chemistry, controlling its catalytic versus chaperone functions. In this study, we have characterized three patient mutations at two conserved active site residues in human ATR, R190C/H, and E193K and obtained crystal structures of R190C and E193K variants, which display only subtle structural changes. All three mutations were found to weaken affinities for the cob(II)alamin substrate and the AdoCbl product and increase K M(ATP) . 31 P NMR studies show that binding of the triphosphate product, formed during the adenosylation reaction, is also weakened. However, although the k cat of this reaction is significantly diminished for the R190C/H mutants, it is comparable with the WT enzyme for the E193K variant, revealing the catalytic importance of Arg-190. Furthermore, although the E193K mutation selectively impairs the chaperone function by promoting product release into solution, its catalytic function might be unaffected at physiological ATP concentrations. In contrast, the R190C/H mutations affect both the catalytic and chaperoning activities of ATR. Because the E193K mutation spares the catalytic activity of ATR, our data suggest that the patients carrying this mutation are more likely to be responsive to cobalamin therapy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗