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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 217 records · Page 12
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Eucalyptus Are Unlikely to Escape Plantations and Invade Surrounding Forests Managed with Prescribed Fire in Southeastern US

Woody biomass production can increase through establishment of non-native tree species exhibiting greater growth potential than traditional native species. Interest in growing Eucalyptus in the southeastern US has raised concern over its potential spread and invasion, which could impact ecosystem properties and functions. Within the matrix of land use where Eucalyptus establishment is being considered in the southeastern US, surrounding pine forests managed with fire represent a likely pathway for invasion. We used greenhouse and field experiments to evaluate the potential invasion risk of Eucalyptus benthamii. We were specifically interested in determining if seeds could successfully germinate in fire-maintained pine forests and if fire-return intervals influenced germination through impacts on litter accumulation and light availability. The greenhouse experiment investigated the influence of light availability on germination success, whereas the field study investigated the influence of time since fire, and thus litter accumulation and light availability, on germination success. Percent germination was similar under non-shaded controls and moderate shade, but complete shade resulted in low germination rates. Germination was lower in the field compared to the greenhouse and was influenced by litter and light availability, which varied according to fire-return intervals. Litter increased, and light availability decreased, with time since burn. Germination was negatively related to litter depth and positively related to light availability, thereby decreasing with time since fire. Germination increased with litter removal but remained positively related to light availability after litter removal. Higher germination with litter removal suggests germination is influenced by litter, but higher germination with increased light availability, regardless of raking, suggests germination is also influenced by light availability. Despite these relationships, no seedlings persisted through the growing season. The low germination rates under a variety of field conditions coupled with the lack of persistence suggests establishment may be unlikely, regardless of the surrounding land matrix.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Preoperative imaging for locoregional staging of bladder cancer

Bladder cancer is the ninth most common cancer, expected to lead to an estimated 17,670 deaths in the United States in 2019. Clinical management and prognosis of bladder cancer mainly depend on the extent of locoregional disease, particularly whether bladder muscle is involved. Therefore, bladder cancer is often divided into superficial, non-muscle-invasive bladder cancer and muscle-invasive bladder cancer; the latter often prompts consideration for cystectomy. While precise staging prior to cystectomy is crucial, the optimal preoperative imaging modality used to stage the disease remains controversial. Transurethral resection of bladder tumor (TURBT) followed by computed tomography (CT) urography is the current recommended approach for staging bladder cancer but suffers from a high rate of understaging. We review the recent literature and compare different imaging modalities for assessing the presence of muscle invasion and lymph node involvement prior to cystectomy and highlight the advantages of each modality.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

AFF4 facilitates melanoma cell progression by regulating c-Jun activity

Melanoma is characterized by high mortality and poor prognosis due to metastasis. AFF4 (AF4/FMR2 family member 4), as a scaffold protein, is a component of the super elongation complex (SEC), and is involved in the progression of tumors, e.g., leukemia, head and neck squamous cell carcinoma (HNSCC). However, few studies on AFF4 have focused on melanoma. Here, AFF4 expression levels and clinicopathological features were evaluated in melanoma tissue samples. Then, we performed cell proliferation, migration and invasion assays in A375 and A2058 cells lines in vitro to evaluate the role of AFF4 in melanoma. The effects of AFF4 knockdown in vivo were characterized via a xenograft mouse model. Finally, the correlation between c-Jun and AFF4 protein levels in melanoma was analyzed by rescue assay and immunohistochemistry (IHC). We found that AFF4 expression was upregulated in melanoma tumor tissues and that AFF4 protein expression was also closely related to the prognosis of patients with cutaneous melanoma. Moreover, AFF4 could promote the invasion and migration of melanoma cells by mediating epithelial to mesenchymal transition (EMT). AFF4 might regulate c-Jun activity to promote the invasion and migration of melanoma cells. Importantly, c-Jun was regulated by the AFF4 promoted melanoma tumorigenesis in vivo. Taken together, AFF4 may be a novel oncogene that promotes melanoma progression through regulation of c-Jun activity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

High expression of Notch2 drives tongue squamous cell carcinoma carcinogenesis

Tongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity. Notch signaling is frequently dysregulated in cancer. However, the role of Notch2 in TSCC is not well understood. The aim of this study was to investigate the effect of abnormal expression of Notch2 in TSCC. The expression of Notch2 was tested in 47 pairs of tissues from tongue cancer and normal samples by using immunohistochemical staining. Tongue cancer cells were transfected with siRNA or plasmid. The proliferation of the cells was tested by the CCK8 assay and colony formation assay. Subcutaneous tumor model was established to observe tumor growth. Transwell assay was used to detect the changes of cell migration and invasion ability. A humanized anti-Notch2 antibody was used to TSCC cells. We found that Notch2 was upregulated in tongue carcinoma tissues. Knocking down the expression of Notch2 by siRNA in the TSCC cell lines decreased proliferation ability both in vitro and in vivo. In addition, migration and invasion abilities were inhibited by knockdown of Notch2 in the TSCC cells. However, overexpression of Notch2 increased tongue cancer cell proliferation, invasion and migration. The humanized anti-Notch2 antibody inhibited TSCC cell growth. The results indicated that Notch2 is an oncogene in tongue squamous cell carcinoma and may become the target of a new approach for treating TSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Development of a recombinant anti-VEGFR2-EPCAM bispecific antibody to improve antiangiogenic efficiency

Highlights: • Targeted therapy can be a useful therapeutic method along with traditional methods for breast cancer treatment. • Decreasing Akt/Nf-Kβ signaling pathway is crucial target in order to decreasing angiogenesis in TNBC. • The recombinant antibody can have inhibitory effects on production IL6,8, MMP2, and MMP9. Tumor progression and metastasis, especially in invasive cancers (such as triple-negative breast cancer [TNBC]), depend on angiogenesis, in which vascular epithelial growth factor (VEGF)/vascular epithelial growth factor receptor [1] has a decisive role, followed by the metastatic spread of cancer cells. Although some studies have shown that anti-VEGFR2/VEGF monoclonal antibodies demonstrated favorable results in the clinic, this approach is not efficient, and further investigations are needed to improve the quality of cancer treatment. Besides, the increased expression of epithelial cell adhesion molecule (EpCAM) in various cancers, for instance, invasive breast cancer, contributes to angiogenesis, facilitating the migration of tumor cells to other parts of the body. Thus, the main goal of our study was to target either VEGFR2 or EpCAM as pivotal players in the progression of angiogenesis in breast cancer. Regarding cancer therapy, the production of bispecific antibodies is easier and more cost-effective compared to monoclonal antibodies, targeting more than one antigen or receptor; for this reason, we produced a recombinant antibody to target cells expressing EpCAM and VEGFR2 via a bispecific antibody to decrease the proliferation and metastasis of tumor cells. Following the cloning and expression of our desired anti-VEGFR2/EPCAM sequence in E. coli, the accuracy of the expression was confirmed by Western blot analysis, and its binding activities to VEGFR2 and EPCAM on MDA-MB-231 and MCF-7 cell lines were respectively indicated by flow cytometry. Then, its anti-proliferative potential was indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assay to evaluate inhibitory effects of the antibody on tumor cells. Subsequently, the data indicated that migration, invasion, and angiogenesis were inhibited in breast cancer cell lines via the bispecific antibody. Furthermore, cytokine analysis indicated that the bispecific antibody could moderate interleukin 8 (IL-8) and IL-6 as key mediators in angiogenesis progression in breast cancer. Thus, our bispecific antibody could be considered as a promising candidate tool to decrease angiogenesis in TNBC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

HMMR is a downstream target of FOXM1 in enhancing proliferation and partial epithelial-to-mesenchymal transition of bladder cancer cells

Our previous that HMMR upregulation independently predicts poor survival in patients with papillary muscle-invasive bladder cancer (MIBC). In this study, we explored its downstream regulations and the potential transcriptional factors activating its expression. MIBC derived T24 cells, and non-MIBC (NMIBC) derived RT4 cells were used for in vitro and in vivo studies. HMMR expression enhanced cell proliferation, the expression of mesenchymal markers, and cell invasion. It induced the nuclear entry of β-catenin, increased its active form in the nuclear part, and elevated the relative TOP/FOP activity. The promoter region of HMMR has a canonical FKH motif. FOXM1 bound to this site and activated HMMR transcription. HMMR knockdown significantly weakened FOXM1 overexpression induced bladder cancer growth, invasion, partial epithelial-to-mesenchymal transition (pEMT), as well as the activation of the Wnt/β-catenin signaling pathway. In conclusion, the findings in this study expanded our understanding of the mechanisms underlying HMMR dysregulation and the functional role of the FOXM1-HMMR axis in bladder cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

The role of fascin in carcinogenesis and embryo implantation

Highlights: • Fascin promotes cancer metastasis. • Fascin interacts with transcription factors necessary for EMT, similar to that in trophoblast cells. • Fascin regulates trophoblast cells' migration and invasion. • Fascin could be implicated in trophoblast-endometrial crosstalk. The cytoskeleton, with its actin bundling proteins, plays crucial roles in a host of cellular function, such as cancer metastasis, antigen presentation and trophoblast migration and invasion, as a result of cytoskeletal remodeling. A key player in cytoskeletal remodeling is fascin. Upregulation of fascin induces the transition of epithelial phenotypes to mesenchymal phenotypes through complex interaction with transcription factors. Fascin expression also regulates mitochondrial F-actin to promote oxidative phosphorylation (OXPHOS) in some cancer cells. Trophoblast cells, on the other hand, exhibit similar physiological functions, involving the upregulation of genes crucial for its migration and invasion. Owing to the similar tumor-like characteristics among cancer and trophoblats, we review recent studies on fascin in relation to cancer and trophoblast cell biology; and based on existing evidence, link fascin to the establishment of the maternal-fetal interface.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Incomplete radiofrequency ablation induced chemoresistance by up-regulating heat shock protein 70 in hepatocellular carcinoma

Highlights: • iRFA treatment inhibited cisplatin-induced pyroptosis of HCC cells. • Heat shock protein 70 was involved in the suppression of NLRP3 activation. • iRFA treatment decreased the cisplatin sensitivity of HCC through regulating HSP70. Radiofrequency ablation (RFA) is a common minimally invasive treatment for hepatocellular carcinoma (HCC). Incomplete RFA (iRFA) due to the sub-lethal heat shock challenge of some cell populations leads to the generation of transformed survivor cells with enhanced chemoresistance. However, the underlying mechanism of iRFA on HCCs chemoresistance remains unknown. In the present study, we investigated the effect of iRFA on HCCs sensitivity to cisplatin. Cells treated with the sub-lethal heat shock challenge were used to mimic iRFA treatment in vitro. An orthotopic implantation HCC model was established and also performed iRFA treatment. Flow cytometry, transwell assay, and cell counting kit-8 assay were used to determine the effect of iRFA treatment on cisplatin-induced HCC cell apoptosis, invasion, and cell viability. ELISA and Western blot were used to detect the effect of iRFA treatment on cisplatin-induced HCC cell pyroptosis. We found that iRFA treatment increased the HCC cell proliferation and invasion ability, and inhibited cisplatin-induced pyroptosis. Further experiments showed that iRFA treatment induced upregulation of HSP70, which inhibited the cisplatin-induced NLRP3 inflammasome activation, leading to inhibition of pyroptosis. HSP70 knockdown or NLRP3 overexpression could reverse the effect of iRFA treatment in vitro. In vivo, HSP70 knockdown reversed the chemosensitivity of HCC to cisplatin, which was decreased by iRFA. In conclusion, we demonstrated that iRFA induced drug resistance by HSP70-mediated inhibition of cell pyroptosis in HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Direct evidence that tumor cells soften when navigating confined spaces.

The mechanical properties of cells strongly regulate many physiological and pathological processes. For example, in cancer, invasive and metastatic tumor cells have often been reported to be softer than nontumor cells, raising speculation that cancer cells might adaptively soften to facilitate migration through narrow tissue spaces. Despite growing interest in targeting cell softening to impede invasion and metastasis, it remains to be directly demonstrated that tumor cells soften as they migrate through confined spaces. Here, we address this open question by combining topographically patterned substrates with atomic force microscopy (AFM). Using a polydimethylsiloxane open-roof microdevice featuring tapered, fibronectin-coated channels, we followed the migration of U2OS cells through various stages of confinement while simultaneously performing AFM indentation. As cells progress from unconfined migration to fully confined migration, cells soften and exclude Yes-associated protein from the nucleus. Superresolution imaging reveals that confinement induces remodeling of actomyosin stress fiber architecture. Companion studies with flat one-dimensional microlines indicate that the changes in cytoarchitecture and mechanics are intrinsically driven by topographical confinement rather than changes in cellular aspect ratio. Our studies represent among the most direct evidence to date that tumor cells soften during confined migration and support cell softening as a mechanoadaptive mechanism during invasion.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

An integrated integral projection model ( IPM 2 ) to disentangle size‐structured harvest and natural mortality

Abstract Body size is one of the most important traits governing individual‐level demographic rates and modulating population‐level processes. Multiple size‐dependent demographic rates can simultaneously change population structure, so distinguishing their individual contributions to overall population dynamics remains a challenge. Disentangling size‐dependent harvest rates from other demographic rates is critical for assessing the impact of removal on populations of invasive species. Inference about invasive populations can be difficult, however, as observations are often collected opportunistically as part of removal programs, rather than experimentally designed. Yet accurate inference is essential for understanding the feasibility of population suppression and optimising management decisions. We develop an integrated integral projection model (IPM 2 ) that leverages the strengths of the integrated population model and integral projection model to enable inference about complex, size‐structured demographic rates from imperfect observations. We apply the IPM 2 in the context of invasive European green crab ( Carcinus maenas ), a species for which individual body size strongly regulates both the observation‐generating process and latent, population dynamics. The IPM 2 facilitates the distinct estimation of green crab size‐structured harvest and natural mortality rates, parameters for which no explicit data is collected and that are unidentifiable in component datasets of the integrated population model. The model represents how the green crab population changes over time, providing the first estimates of size‐structured abundance of this high‐priority species. By forecasting the stable size distribution and equilibrium population size under varying removal efforts, we demonstrate that extremely high levels of removal effort can reduce the equilibrium green crab population size. Yet these high mortality rates also shift the stable size distribution and increase the equilibrium abundance of smaller crabs, since size‐selective removal alters intraspecific interactions. The ecological outcome of this shift in size structure will be variable, as green crab size modulates only some of its interactions with other species. These results highlight the value of the IPM 2 framework for inferring complex population dynamics with information needs that outpace information in individual observational datasets, providing a path forward for accurate assessment of conservation programs.

Keller, Abigail G. [Department of Environment Scie↗
DOE OSTI2022

NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. Methods A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. Results Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53–0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47–0.56), invasive ventilation (OR: 0.59 95% CI: 0.55–0.64), AKI (OR: 0.67 95% CI: 0.63–0.72), or ECMO (OR: 0.51 95% CI: 0.36–0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. Conclusions Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Measurement techniques using the electron beam profile scanner at the Fermilab Main Injector

This work presents techniques for non-invasive transverse profile measurements of high-intensity proton beams using an Electron Beam Profile Scanner (EBPS). The EBPS utilizes low-energy electrons as a probe to analyze the transverse size of proton beams, allowing for potential analysis on a single-bunch basis. Recent upgrades to the Fermilab Main Injector have enhanced beam power on target to 1 MW, with future developments targeting 2 MW. The higher beam power has increased the demand for non-invasive diagnostics, as invasive methods can disrupt operations.The techniques presented include 1) the slow scan technique, which serves as a proof of concept for the probe beam, 2) the one-shot scan technique for measuring horizontal beam profiles, and 3) the raster scan technique for analyzing horizontal beam profiles as a function of the longitudinal distribution of the beam. The profiles obtained will be crucial for studying and understanding instabilities in high-power, high-intensity proton beams. This will contribute to optimizing the operation of high-power proton accelerators by minimizing beam loss, activation, and damage to both the diagnostics and the accelerator components.

Mwaniki, Matilda [IIT, Chicago]↗
DOE OSTI2022

Intracardiac Electrical Imaging using the 12-lead ECG: A Machine Learning Approach using Synthetic Data

Current state-of-the-art techniques for non-invasive imaging of cardiac electrical phenomena require voltage recordings from dozens of different torso locations and anatomical models built from expensive medical diagnostic imaging procedures. Here this study aimed to assess if recent machine learning advances could alternatively reconstruct electroanatomical maps at clinically relevant resolutions using only the standard 12-lead electrocardiogram (ECG) as input. To that end, a computational study was conducted to generate a dataset of over 16000 detailed cardiac simulations, which was then used to train neural network (NN) architectures designed to exploit both spatial and temporal correlations in the ECG signal. Analysis over a validation set showed average errors in activation map reconstruction below 1.7 msec over 75 intracardiac locations. Furthermore, phenotypical patterns of activation and the morphology of the activation potential were correctly reconstructed. The approach offers opportunities to stratify patients non-invasively, both retrospectively and prospectively, using metrics otherwise only available through invasive clinical procedures.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

BRAVE_EBC-TMT.1.0

Exhaled breath condensate (EBC) represents a low-cost and non-invasive means of examining respiratory health. EBC has been used to discover and validate exhaled volatile and non-volatile biomarkers of disease related to the respiratory system distress such as asthma, COPD, lung cancer, and secondary infections. One newly emerging utilization of EBC, is proteomics analysis, which can provide an unbiased snapshot into ongoing biological processes in the airway. Fully characterizing the biological landscape of EBC collections is challenging though, due to sample variability, and low detection sensitivity. EBC is primarily composed of condensed water, causing technical challenges with detecting key macromolecules from the dilute sample matrix; therefore, high sensitivity techniques are required to unlock the full capability of EBC as a method for non-invasive biomarker detection. To overcome some of these technical challenges for proteomic analyses, we applied our recently developed microscale proteomic techniques and developed a novel TMT based approach which enabled reliable, relative quantification with significantly improved detection of low abundance peptides/proteins across multiple healthy volunteer EBC samples. Our EBC collection design includes longitudinal EBC collections from five individual healthy volunteers on three separate days of the week with triplicate, back-to-back donations each day. Here, we report a total of 235 quantifiable proteins corresponding to 1,877 non-redundant peptides for evaluating sample collection reproducibility and establishing a healthy (human host) baseline EBC biomarker proteome studies. This work will pave the way for further investigations of EBC protein expression profiles and showcase the value of using non-invasive collection method techniques for clinically relevant biomarker discovery. This research was supported by the LDRD Biomedical Resilience And Readiness in AdVerse Operating Environments (BRAVE) Project (73748), and was conducted at Pacific Northwest National Laboratory (PNNL) in Richland, WA. PNNL is a multiprogram national laboratory operated by Battelle for the Department of Energy (DOE) under Contract DE-AC05-76RLO 1830.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Neonatal respiratory support strategies—short and long-term respiratory outcomes

Mechanical ventilation (MV), although life-saving, is associated with chronic respiratory morbidity in both preterm and term born infants. New ventilation modes have been developed with the aim of minimising lung injury. These include invasive and non-invasive respiratory support strategies, techniques for less invasive surfactant administration (LISA) and closed-loop automated oxygen control (CLAC) systems. Increasingly, newborn infants with signs of respiratory distress are stabilised on continuous positive airway pressure (CPAP) and receive LISA. Early CPAP when compared to mechanical ventilation reduced the incidence of BPD and respiratory morbidity at 18 to 22 months corrected age. Nasal intermittent positive pressure ventilation reduced treatment failure rates compared to CPAP, but not bronchopulmonary dysplasia (BPD). LISA compared with intubation and surfactant delivery reduced BPD, but there is no evidence from randomised trials regarding long-term respiratory and neurodevelopmental outcomes. Synchronisation of positive pressure inflations with the infant's respiratory efforts used with volume targeting should be applied for infants requiring intubation as this strategy reduces BPD. A large RCT with long term follow up data demonstrated that prophylactic high frequency oscillatory ventilation (HFOV) improved respiratory and functional outcomes at school age, but those effects were not maintained after puberty. CLAC systems appear promising, but their effect on long term clinical outcomes has not yet been explored in randomised trials. Further studies are required to determine the role of newer ventilation modes such as neurally adjusted ventilator assist (NAVA). All such respiratory support strategies should be tested in randomised controlled trials powered to assess long-term outcomes.

Kaltsogianni, Ourania↗
DOE OSTI2022

Evaluation of intracoronary hemodynamics identifies perturbations in vorticity

Coronary artery disease (CAD) is highly prevalent and associated with adverse events. Challenges have emerged in the treatment of intermediate coronary artery stenoses. These lesions are often interrogated with fractional flow reserve (FFR) testing to determine if a stenosis is likely to be causative for ischemia in a cardiac territory. This invasive test requires insertion of a pressure wire into a coronary vessel. Recently computational fluid dynamics (CFD) has been used to noninvasively assess fractional flow reserve in vessels reconstructed from medical imaging data. However, many of these simulations are unable to provide additional information about intravascular hemodynamics, including velocity, endothelial shear stress (ESS), and vorticity. We hypothesized that vorticity, which has demonstrated utility in the assessment of ventricular and aortic diseases, would also be an important hemodynamic factor in CAD. Three-dimensional (3D), patient-specific coronary artery geometries that included all vessels >1 mm in diameter were created from angiography data obtained from 10 patients who underwent diagnostic angiography and FFR testing (n = 9). A massively parallel CFD solver (HARVEY) was used to calculate coronary hemodynamic parameters including pressure, velocity, ESS, and vorticity. These simulations were validated by comparing velocity flow fields from simulation to both velocities derived from in vitro particle image velocimetry and to invasively acquired pressure wire-based data from clinical testing. There was strong agreement between findings from CFD simulations and particle image velocimetry experimental testing (p < 0.01). CFD-FFR was also highly correlated with invasively measured FFR (ρ = 0.77, p = 0.01) with an average error of 5.9 ± 0.1%. CFD-FFR also had a strong inverse correlation with the vorticity (ρ = -0.86, p = 0.001). Simulations to determine the effect of the coronary stenosis on intravascular hemodynamics demonstrated significant differences in velocity and vorticity (both p < 0.05). Further evaluation of an angiographically normal appearing non-FFR coronary vessel in patients with CAD also demonstrated differences in vorticity when compared with FFR vessels (p < 0.05). The use of highly accurate 3D CFD-derived intravascular hemodynamics provides additional information beyond pressure measurements that can be used to calculate FFR. Vorticity is one parameter that is modified by a coronary stenosis and appears to be abnormal in angiographically normal vessels in patients with CAD, highlighting a possible use-case in preventative screening for early coronary disease.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Use of Micro-Gravity Sensors for External Fluid Level Monitoring in Waste and Nuclear Related Applications - 20315

There are a number of applications in nuclear energy and hazardous waste disposal that require monitoring of fluids under extreme environments, including high levels of temperature, pressure, toxicity and radioactivity. Many of these applications will benefit from a monitoring technique that is external and non-invasive. Currently the sensors used are invasive, must reside inside the pressurized vessels and must penetrate the vessel walls, which can create a weakness in the vessel. Additionally, instruments that are used inside such containers must be exceptionally hardened to the environment. Information Systems Laboratories (ISL) has developed an external mass (gravimetric) measuring technique for monitoring nuclear coolant in Small Modular Reactors (SMRs), which will also work for measuring fluid levels in waste tanks, that avoids the problems inherent in invasive sensors. It utilizes a COTS gravitational sensor of unprecedented accuracy, leveraged via proper sensor placement geometry, to detect fluid changes of small amplitude from an outside position, obviating the need to penetrate the vessel. The technique is called Gravisense{sup TM}. ISL has proven via simulation and experiment that this concept can be usefully applied to monitoring fluid levels in both nuclear reactors and large waste tanks. Numerical simulation algorithms were developed to calculate the gravity effect of small changes in water level, which were verified by experiments at the NIST Physical Simulator facility at the Oregon State University. The measured ultralow noise levels of the superconducting gravimeter type which utilizes a Niobium sphere suspended in a magnetic field to attain its phenomenal accuracy, demonstrated that fluid levels in SMRs can be measured at least to within 3 cm. Furthermore, the method can distinguish between a contained leak (from reactor to containment vessel) from an external leak (from reactor to outside of containment). Additionally, simulations of waste canisters that hold spent fuel rods show that the fluid level measuring accuracy can potentially do better than 1 cm accuracy by measuring from below the vessel, and judicious placement of sensors on top of large waste tanks can potentially achieve a very impressive 2 mm measurement accuracy. These encouraging results prove that the Gravisense{sup TM} technique for fluid determination can be very useful in nuclear energy generation, testing, and research, as well as in waste monitoring situations that are difficult to monitor via traditional sensing technology. We believe that the next step should be to test the technique on canisters of the type that are currently storing waste in various DOE locations. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2025

Persistent urinary metabolic signatures in children with type 1 diabetes

There are an estimated 3.7 million people with undiagnosed type 1 diabetes (T1D), living primarily in poor areas of the globe. Therefore, there is a need for non-invasive, affordable tests to provide accurate diagnosis despite the time post-disease onset and fasting state. Here, we studied persistent urinary T1D biomarkers that can be used to develop such tests. Here, we analyzed the urine metabolomes of three independent cohorts of samples collected within 48 h (from Indiana University), and 1 year (from University of Colorado) and 1–10 years (6 years in average) (from Children’s National Medical Center) post-diagnosis. Samples were submitted to gas chromatography-mass spectrometry and machine learning an0alyses to determine diagnostic metabolite panels. The data were also mapped into a metabolic pathway to understand persistently regulated processes in T1D. Seven metabolites showed consistent increases in all three cohorts: d-glucose, d-mannose, myo-inositol, 3-hydroxyisobutyric acid, gluconolactone, d-gluconic acid, and d-glucuronic acid. A combination of machine learning analysis and metabolite ratios as biomarker candidates diagnosed T1D with high sensitivity and specificity across different cohorts and times. Mapping the regulated metabolites into a pathway showed impairment in glycolysis and overflow of glucose towards other pathways in subjects with T1D that was persistent over time. We identified and cross-validated highly specific and sensitive urinary biomarkers. This opens opportunities to develop affordable, robust, and non-invasive tests. The results also show that most of the biomarkers were signatures of dysregulated glucose metabolism.

Type 1 diabetes↗