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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 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Involvement of the Streptococcus mutans PgfE and GalE 4-epimerases in protein glycosylation, carbon metabolism, and cell division

Streptococcus mutans is a key pathogen associated with dental caries and is often implicated in infective endocarditis. This organism forms robust biofilms on tooth surfaces and can use collagen-binding proteins (CBPs) to efficiently colonize collagenous substrates, including dentin and heart valves. One of the best characterized CBPs of S. mutans is Cnm, which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of 4 enzymes: PgfS, PgfM1, PgfE, and PgfM2. Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells, and attenuated virulence in the Galleria mellonella invertebrate model. The present study aimed to better understand Cnm glycosylation and characterize the predicted 4-epimerase, PgfE. Using a truncated Cnm variant containing only 2 threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. Compositional analysis, complemented with lectin blotting, identified the HexNAc2 moieties as GlcNAc and GalNAc. Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, nuclear magnetic resonance, and capillary electrophoresis demonstrated that GalE is a UDP-Glc-4-epimerase, while PgfE is a GlcNAc-4-epimerase. While PgfE exclusively participates in protein O-glycosylation, we found that GalE affects galactose metabolism and cell division. Furthermore, this study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm.

4-epimerases↗
DOE OSTI2023

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Melanoxetin: A Hydroxylated Flavonoid Attenuates Oxidative Stress and Modulates Insulin Resistance and Glycation Pathways in an Animal Model of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin’s therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

Rocha, Sónia (ORCID:0000000177862731)↗
DOE OSTI2022

Dual-Biometric Human Identification Using Radar Deep Transfer Learning

Accurate human identification using radar has a variety of potential applications, such as surveillance, access control and security checkpoints. Nevertheless, radar-based human identification has been limited to a few motion-based biometrics that are solely reliant on micro-Doppler signatures. This paper proposes for the first time the use of combined radar-based heart sound and gait signals as biometrics for human identification. The proposed methodology starts by converting the extracted biometric signatures collected from 18 subjects to images, and then an image augmentation technique is applied and the deep transfer learning is used to classify each subject. A validation accuracy of 58.7% and 96% is reported for the heart sound and gait biometrics, respectively. Next, the identification results of the two biometrics are combined using the joint probability mass function (PMF) method to report a 98% identification accuracy. To the best of our knowledge, this is the highest reported in the literature to date. Lastly, the trained networks are tested in an actual scenario while being used in an office access control platform to identify different human subjects. We report an accuracy of 76.25%.

47 OTHER INSTRUMENTATION↗
DOE OSTI2020

Quantifying Human Behavior and Decision Errors in Security Screening Operations

The potential for human errors in conducting security related screening operations can lead to inadvertent and adverse decision outcomes. This paper overviews an initial mathematical framework designed to model and quantify the various human factors and decision outcomes that may occur in conducting security screening operations, such as U.S. port of entry radiological and nuclear (rad/nuc) security screening. This framework is based on the Human Error Assessment and Reduction (HEART) technique. As applied here, the framework incorporates a set of rules for human engagement, including a prescribed concept of operations (CONOPS) and deviations that may occur from this established CONOPS due to inadvertent personnel decision errors. We also review some of the various factors that may adversely influence such decisions by security screening personnel. Some of these factors include current workload, environmental conditions, training, and various other intangible factors. Using the HEART methodology, we translate each of these factors into error producing conditions, their effects on error, an assessed proportion of effects, and finally the overall probability of human error at each stage of the screening process. We then include a small scale example to demonstrate the methodology and results based on an assumed set of input conditions at a notional port of entry.

Brigantic, Robert T.↗
DOE OSTI2019

Cardiac Sarcoidosis

Purpose of Review: In this state-of-the-art review, we highlight our current understanding of diagnosis, assessment, and management of cardiac sarcoidosis (CS), focusing on recently published data and expert consensus statement guidelines. Recent Findings: Academic interest in cardiac sarcoidosis research has increased over the past decade along with increased clinical awareness among clinicians. In 2014, the Heart Rhythm Society published the first expert consensus statement on diagnosing and managing arrhythmias associated with CS. Cardiac magnetic resonance has emerged as a valuable tool both for diagnosing CS and predicting risk of life-threatening ventricular arrhythmias based on burden of late gadolinium enhancement. Cardiac fluorodeoxyglucose-positron emission tomography now plays a role in diagnosis, risk stratification, and assessing response to immunosuppressive therapy. Summary: Collaborative, multidisciplinary research efforts are needed to further our understanding of this rare, complex disease. Two large multicenter prospective registries—the international Cardiac Sarcoidosis Consortium and the Canadian Cardiac Sarcoidosis Research Group—are enrolling patients to help provide insights into the natural history of the disease and current treatment strategies. Future research should focus on randomized controlled trials comparing different treatment strategies and identifying and testing novel therapeutic agents.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity

Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to “scaffold” regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS 2 ) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. Here, the in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo. Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BRS and expand the range of lesions that can be treated using transient implants.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Safety Margins for the Delineation of the Left Anterior Descending Artery in Patients Treated for Breast Cancer

Cardiac toxicity after breast cancer (BC) radiation therapy is partly due to the large radiation doses to coronary arteries. The left anterior descending artery (LAD) is particularly exposed. A first step in achieving robust dose constraints to the LAD during treatment planning is homogeneous delineation based on guidelines. LAD delineation can be problematic due to heart movements. The aim of the study was to establish a safety margin for delineation of the LAD in patients with BC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Cultured cardiac fibroblasts and myofibroblasts express Sushi Containing Domain 2 and assemble a unique fibronectin rich matrix

Highlights: • Cultured cardiac fibroblasts and myofibroblasts derived from normal human hearts express the novel marker SUSD2. • Under high density culture conditions, human cardiac myofibroblasts deposit a matrix scaffold rich in fibronectin. • Cultured dermal fibroblasts do not express SUSD2 and did not for form scaffolds in vitro. Cardiac fibroblasts and myofibroblasts assemble and maintain extracellular matrix during normal development and following injury. Culture expansion of these cells yield a bioengineered matrix that could lead to intriguing therapeutic opportunities. For example, we reported that cultured rat cardiac fibroblasts form a matrix that can be used to delivery therapeutic stem cells. Furthermore, we reported that matrix derived from cultured human cardiac fibroblasts/myofibroblasts converted monocytes into macrophages that express interesting anti-inflammatory and pro-angiogenic properties. Expanding these matrix investigations require characterization of the source cells for quality control. In these efforts, we observed and herein report that Sushi Containing Domain 2 (SUSD2) is a novel and consistent marker for cultured human cardiac fibroblast and myofibroblasts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Noonan syndrome patient-specific induced cardiomyocyte model carrying SOS1 gene variant c.1654A>G

Noonan syndrome (NS) is a dominant autosomal genetic disorder, associated with mutations in several genes that exhibit multisystem abnormal development including cardiac defects. NS associated with the Son of Sevenless homolog 1 (SOS1) gene mutation attributes to the development of cardiomyopathy and congenital heart defects. Since the treatment option for NS is very limited, an in vitro disease model with SOS1 gene mutation would be beneficial for exploring therapeutic possibilities for NS. We reprogrammed cardiac fibroblasts obtained from a NS patient and normal control skin fibroblasts (C-SF) into induced pluripotent stem cells (iPSCs). We identified NS-iPSCs carry a heterozygous single nucleotide variation in the SOS1 gene at the c.1654A > G. Furthermore, the control and NS-iPSCs were differentiated into induced cardiomyocytes (iCMCs), and the electron microscopic analysis showed that the sarcomeres of the NS-iCMCs were highly disorganized. FACS analysis showed that 47.5% of the NS-iCMCs co-expressed GATA4 and cardiac troponin T proteins, and the mRNA expression levels of many cardiac related genes, studied by qRT-PCR array, were significantly reduced when compared to the control C-iCMCs. We report for the first time that NS-iPSCs carry a single nucleotide variation in the SOS1 gene at the c.1654A>G were showing significantly reduced cardiac genes and proteins expression as well as structurally and functionally compromised when compared to C-iCMCs. These iPSCs and iCMCs can be used as a modeling platform to unravel the pathologic mechanisms and also the development of novel drug for the cardiomyopathy in patients with NS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Identification and characterization of distinct cell cycle stages in cardiomyocytes using the FUCCI transgenic system

Understanding the regulatory mechanism by which cardiomyocyte proliferation transitions to endoreplication and cell cycle arrest during the neonatal period is crucial for identifying proproliferative factors and developing regenerative therapies. }We used a transgenic mouse model based on the fluorescent ubiquitination-based cell cycle indicator (FUCCI) system to isolate and characterize cycling cardiomyocytes at different cell cycle stages at a single-cell resolution. Single-cell transcriptome analysis of cycling and noncycling cardiomyocytes was performed at postnatal days 0 (P0) and 7 (P7). }The FUCCI system proved to be efficient for the identification of cycling cardiomyocytes with the highest mitotic activity at birth, followed by a gradual decline in the number of cycling and mitotic cardiomyocytes during the neonatal period. Cardiomyocytes showed premature cell cycle exit at G1/S shortly after birth and delayed G1/S progression during endoreplication at P7. Single-cell RNA-seq confirmed previously described signaling pathways involved in cardiomyocyte proliferation (Erbb2 and Hippo/YAP), and maturation-related transcriptional changes during postnatal development, including the metabolic switch from glycolysis to fatty acid oxidation in cardiomyocytes. Importantly, we generated transcriptional profiles specific to cell division and endoreplication in cardiomyocytes at different developmental stages that may facilitate the identification of genes important for adult cardiomyocyte proliferation and heart regeneration. }In conclusion, the FUCCI mouse provides a valuable system to study cardiomyocyte cell cycle activity at single cell resolution that can help to decipher the switch from cardiomyocyte proliferation to endoreplication, and to revert this process to facilitate endogenous repair.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

First comprehensive identification of cardiac proteins with putative increased O-GlcNAc levels during pressure overload hypertrophy

Protein posttranslational modifications (PTMs) by O-GlcNAc globally rise during pressure-overload hypertrophy (POH). However, a major knowledge gap exists on the specific proteins undergoing changes in O-GlcNAc levels during POH primarily because this PTM is low abundance and easily lost during standard mass spectrometry (MS) conditions used for protein identification. Methodologies have emerged to enrich samples for O-GlcNAcylated proteins prior to MS analysis. Accordingly, our goal was to identify the specific proteins undergoing changes in O-GlcNAc levels during POH. We used C57/Bl6 mice subjected to Sham or transverse aortic constriction (TAC) to create POH. From the hearts, we labelled the O-GlcNAc moiety with tetramethylrhodamine azide (TAMRA) before sample enrichment by TAMRA immunoprecipitation (IP). We used LC-MS/MS to identify and quantify the captured putative O-GlcNAcylated proteins. We identified a total of 700 putative O-GlcNAcylated proteins in Sham and POH. Two hundred thirty-three of these proteins had significantly increased enrichment in POH over Sham suggesting higher O-GlcNAc levels whereas no proteins were significantly decreased by POH. We examined two MS identified metabolic enzymes, CPT1B and the PDH complex, to validate by immunoprecipitation. We corroborated increased O-GlcNAc levels during POH for CPT1B and the PDH complex. Enzyme activity assays suggests higher O-GlcNAcylation increases CPT1 activity and decreases PDH activity during POH. In summary, we generated the first comprehensive list of proteins with putative changes in O-GlcNAc levels during POH. Our results demonstrate the large number of potential proteins and cellular processes affected by O-GlcNAc and serve as a guide for testing specific O-GlcNAc-regulated mechanisms during POH.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

How Reproducible are Surface Areas Calculated from the BET Equation?

Abstract Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer–Emmett–Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of micro‐ and mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already‐measured raw adsorption isotherms were provided to sixty‐one labs, who were asked to calculate the corresponding BET areas. This round‐robin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called “BET surface identification” (BETSI), expands on the well‐known Rouquerol criteria and makes an unambiguous BET area assignment possible.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Compute in‐Memory with Non‐Volatile Elements for Neural Networks: A Review from a Co‐Design Perspective

Abstract Deep learning has become ubiquitous, touching daily lives across the globe. Today, traditional computer architectures are stressed to their limits in efficiently executing the growing complexity of data and models. Compute‐in‐memory (CIM) can potentially play an important role in developing efficient hardware solutions that reduce data movement from compute‐unit to memory, known as the von Neumann bottleneck. At its heart is a cross‐bar architecture with nodal non‐volatile‐memory elements that performs an analog multiply‐and‐accumulate operation, enabling the matrix‐vector‐multiplications repeatedly used in all neural network workloads. The memory materials can significantly influence final system‐level characteristics and chip performance, including speed, power, and classification accuracy. With an over‐arching co‐design viewpoint, this review assesses the use of cross‐bar based CIM for neural networks, connecting the material properties and the associated design constraints and demands to application, architecture, and performance. Both digital and analog memory are considered, assessing the status for training and inference, and providing metrics for the collective set of properties non‐volatile memory materials will need to demonstrate for a successful CIM technology.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Exciton Transport in Perovskite Materials

Halide perovskites have emerged as promising materials for a wide variety of optoelectronic applications, including solar cells, light‐emitting devices, photodetectors, and quantum information applications. In addition to their desirable optical and electronic properties, halide perovskites provide tremendous synthetic flexibility through variation of not only their chemical composition but also their structure and morphology. At the heart of their use in optoelectronic technologies is the interaction of light with electronic excitations in the form of excitons. This review discusses the properties and behavior of excitons in halide perovskite materials, with a particular emphasis on low‐dimensional perovskites and the effects of nanoscale morphology on excitonic behavior. The basic theory of excitonic energy migration in semiconductor nanomaterials is introduced, and novel observations in halide perovskite nanomaterials that have evolved our current understanding are explored. Lastly, many important questions that remain unanswered are presented and exciting emerging directions in low‐dimensional perovskite exciton physics are discussed.

2D materials↗