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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Odor exposure during imprinting periods increases odorant-specific sensitivity and receptor gene expression in coho salmon ( Oncorhynchus kisutch )

ABSTRACT Pacific salmon are well known for their homing migrations; juvenile salmon learn odors associated with their natal streams prior to seaward migration, and then use these retained odor memories to guide them back from oceanic feeding grounds to their river of origin to spawn several years later. This memory formation, termed olfactory imprinting, involves (at least in part) sensitization of the peripheral olfactory epithelium to specific odorants. We hypothesized that this change in peripheral sensitivity is due to exposure-dependent increases in the expression of odorant receptor (OR) proteins that are activated by specific odorants experienced during imprinting. To test this hypothesis, we exposed juvenile coho salmon, Oncorhynchus kisutch, to the basic amino acid odorant l-arginine during the parr–smolt transformation (PST), when imprinting occurs, and assessed sensitivity of the olfactory epithelium to this and other odorants. We then identified the coho salmon ortholog of a basic amino acid odorant receptor (BAAR) and determined the mRNA expression levels of this receptor and other transcripts representing different classes of OR families. Exposure to l-arginine during the PST resulted in increased sensitivity to that odorant and a specific increase in BAAR mRNA expression in the olfactory epithelium relative to other ORs. These results suggest that specific increases in ORs activated during imprinting may be an important component of home stream memory formation and this phenomenon may ultimately be useful as a marker of successful imprinting to assess management strategies and hatchery practices that may influence straying in salmon.

Dittman, Andrew H. (ORCID:000000016482359X)↗
DOE OSTI2018

Comparative Approach of MRI-Based Brain Tumor Segmentation and Classification Using Genetic Algorithm

The detection of a brain tumor and its classification from modern imaging modalities is a primary concern, but a time-consuming and tedious work was performed by radiologists or clinical supervisors. The accuracy of detection and classification of tumor stages performed by radiologists is depended on their experience only, so the computer-aided technology is very important to aid with the diagnosis accuracy. In this study, to improve the performance of tumor detection, we investigated comparative approach of different segmentation techniques and selected the best one by comparing their segmentation score. Further, to improve the classification accuracy, the genetic algorithm is employed for the automatic classification of tumor stage. The decision of classification stage is supported by extracting relevant features and area calculation. The experimental results of proposed technique are evaluated and validated for performance and quality analysis on magnetic resonance brain images, based on segmentation score, accuracy, sensitivity, specificity, and dice similarity index coefficient. The experimental results achieved 92.03% accuracy, 91.42% specificity, 92.36% sensitivity, and an average segmentation score between 0.82 and 0.93 demonstrating the effectiveness of the proposed technique for identifying normal and abnormal tissues from brain MR images. The experimental results also obtained an average of 93.79% dice similarity index coefficient, which indicates better overlap between the automated extracted tumor regions with manually extracted tumor region by radiologists.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

WE-DE-201-11: Sensitivity and Specificity of Verification Methods Based On Total Reference Air Kerma (TRAK) Or On User Provided Dose Points for Graphically Planned Skin HDR Brachytherapy

Purpose: To investigate the sensitivity and specificity of a novel verification methodology for image-guided skin HDR brachytherapy plans using a TRAK-based reasonableness test, compared to a typical manual verification methodology. Methods: Two methodologies were used to flag treatment plans necessitating additional review due to a potential discrepancy of 3 mm between planned dose and clinical target in the skin. Manual verification was used to calculate the discrepancy between the average dose to points positioned at time of planning representative of the prescribed depth and the expected prescription dose. Automatic verification was used to calculate the discrepancy between TRAK of the clinical plan and its expected value, which was calculated using standard plans with varying curvatures, ranging from flat to cylindrically circumferential. A plan was flagged if a discrepancy >10% was observed. Sensitivity and specificity were calculated using as a criteria for true positive that >10% of plan dwells had a distance to prescription dose >1 mm different than prescription depth (3 mm + size of applicator). All HDR image-based skin brachytherapy plans treated at our institution in 2013 were analyzed. Results: 108 surface applicator plans to treat skin of the face, scalp, limbs, feet, hands or abdomen were analyzed. Median number of catheters was 19 (range, 4 to 71) and median number of dwells was 257 (range, 20 to 1100). Sensitivity/specificity were 57%/78% for manual and 70%/89% for automatic verification. Conclusion: A check based on expected TRAK value is feasible for irregularly shaped, image-guided skin HDR brachytherapy. This test yielded higher sensitivity and specificity than a test based on the identification of representative points, and can be implemented with a dedicated calculation code or with pre-calculated lookup tables of ideally shaped, uniform surface applicators.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

How Advances in Imaging Will Affect Precision Radiation Oncology

Radiation oncology is 1 of the most structured disciplines in medicine. It is of a highly technical nature with reliance on robotic systems to deliver intervention, engagement of diverse expertise, and early adoption of digital approaches to optimize and execute the application of this highly effective cancer treatment. As a localized intervention, the dependence on sensitive, specific, and accurate imaging to define the extent of disease, its heterogeneity, and adjacency to normal tissues directly affects the therapeutic ratio. Image-based in vivo temporal monitoring of the response to treatment enables adaptation and further affects the therapeutic ratio. Thus, more precise intervention will enable fractionation schedules that better interoperate with advances such as immunotherapy. In the data set–rich era that promises precision and personalized medicine, the radiation oncology field will integrate these new data into highly protocoled pathways of care that begin with multimodality prediction and enable patient-specific adaptation of therapy based on quantitative measures of the individual's dose–volume temporal trajectory and midtherapy predictions of response. In addition to advancements in computed tomography imaging, emerging technologies, such as ultra-high-field magnetic resonance and molecular imaging will bring new information to the design of treatments. Next-generation image guided radiation therapy systems will inject high specificity and sensitivity data and stimulate adaptive replanning. In addition, a myriad of pre- and peritherapeutic markers derived from advances in molecular pathology (eg, tumor genomics), automated and comprehensive imaging analytics (eg, radiomics, tumor microenvironment), and many other emerging biomarkers (eg, circulating tumor cell assays) will need to be integrated to maximize the benefit of radiation therapy for an individual patient. We present a perspective on the promise and challenges of fully exploiting imaging data in the pursuit of personalized radiation therapy, drawing from the presentations and broader discussions at the 2016 American Society of Therapeutic Radiation Oncology–National Cancer Institute workshop on Precision Medicine in Radiation Oncology (Bethesda, MD).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Engineering sensitivity and specificity of AraC-based biosensors responsive to triacetic acid lactone and orsellinic acid

Abstract We previously described the design of triacetic acid lactone (TAL) biosensor ‘AraC-TAL1’, based on the AraC regulatory protein. Although useful as a tool to screen for enhanced TAL biosynthesis, this variant shows elevated background (leaky) expression, poor sensitivity and relaxed inducer specificity, including responsiveness to orsellinic acid (OA). More sensitive biosensors specific to either TAL or OA can aid in the study and engineering of polyketide synthases that produce these and similar compounds. In this work, we employed a TetA-based dual-selection to isolate new TAL-responsive AraC variants showing reduced background expression and improved TAL sensitivity. To improve TAL specificity, OA was included as a ‘decoy’ ligand during negative selection, resulting in the isolation of a TAL biosensor that is inhibited by OA. Finally, to engineer OA-specific AraC variants, the iterative protein redesign and optimization computational framework was employed, followed by 2 rounds of directed evolution, resulting in a biosensor with 24-fold improved OA/TAL specificity, relative to AraC-TAL1.

Wang, Zhiqing↗
DOE OSTI2022

A sensitive and specific genetically-encoded potassium ion biosensor for in vivo applications across the tree of life

Potassium ion (K + ) plays a critical role as an essential electrolyte in all biological systems. Genetically-encoded fluorescent K + biosensors are promising tools to further improve our understanding of K + -dependent processes under normal and pathological conditions. Here, we report the crystal structure of a previously reported genetically-encoded fluorescent K + biosensor, GINKO1, in the K + -bound state. Using structure-guided optimization and directed evolution, we have engineered an improved K + biosensor, designated GINKO2, with higher sensitivity and specificity. We have demonstrated the utility of GINKO2 for in vivo detection and imaging of K + dynamics in multiple model organisms, including bacteria, plants, and mice.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

WE-EF-210-05: Diagnosis and Quantification of Liver Steatosis with Quantitative Ultrasound Backscatter Technique

Purpose: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, affects 30% of adult Americans and may progress to more serious diseases. Liver biopsy is the standard method for diagnosing NAFLD. MRI can accurately diagnose and quantify hepatic steatosis but is expensive. Sonography with qualitative interpretation by radiologists is lower cost, more accessible but less sensitive for detection. The objective of this study, using MRI proton density fat fraction (PDFF) as reference, is to assess the accuracy for diagnosing and quantifying steatosis with two quantitative US parameters-- backscatter coefficient (BSC) and attenuation coefficient (AC)--derived from RF signals using the calibration phantom technique. Methods: We performed a prospective, cross-sectional analysis of a cohort of adults (n=204) with NAFLD (MRI-PDFF≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and BSC and AC US analyses of the liver on the same day. Patients were randomly assigned to training (n=102, mean age 51±17 years, mean body mass index 31±7 kg/m{sup 2}) and validation (n=102, mean age 49±17 years, body mass index 30±6 kg/m{sup 2}) groups; 69% of patients in each group had NAFLD. Results: BSC provided AUC 0.98 (95% CI 0.95–1.00, p<0.0001) for diagnosis of NAFLD; the optimal BSC cut-off provided sensitivity, specificity, positive and negative predictive values (PPV, NPV) of 87%, 91%, 95%, and 76%, respectively. AC provided AUC 0.89 (95% CI 0.81–0.96, p<0.0001) for diagnosis of steatosis; the optimal AC cut-off provided sensitivity, specificity, PPV, NPV of 80%, 84%, 92%, and 66%, respectively. BSC and AC both correlated significantly with MRI-PDFF (P<0.0001). Conclusion: QUS BSC and AC can accurately diagnose and quantify hepatic steatosis, using MRI-PDFF as reference. With further validation, QUS may emerge as an inexpensive, widely available tool for NAFLD assessment. General support: NIH R01 CA111289, K23 -DK090303, AmerGastroAssoc Found, TF Williams Scholarship, S3000 scanner loaned by Siemens, Sucampo, JA Hartford Found, Atlantic Philanthropies Amer Gastroenterological Assoc. Agencies had no role in design/conduct of study, collection, management, analysis or interpretation of the data; preparation, review, or approval of the manuscript.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Polymerase chain reaction for the in vitro detection of the pESI plasmid associated with the globally circulating Salmonella Infantis outbreak strain

Abstract A globally circulating strain of Salmonella enterica serotype Infantis containing the pESI plasmid has increased in prevalence in poultry meat samples and cases of human infections. In this study, a polymerase chain reaction (PCR) protocol was designed to detect the pESI plasmid and confirm the Infantis serotype of Salmonella isolates. Primers were tested bioinformatically to predict specificity, sensitivity, and precision. A total of 54 isolates of Salmonella serotypes Infantis, Senftenberg, and Alachua were tested, with and without the pESI plasmid carriage. Isolates of 31 additional serotypes were also screened to confirm specificity to Infantis. Specificity, sensitivity, and precision of each primer were >0.95. All isolates tested produced the expected band sizes. This PCR protocol provides a rapid and clear result for the detection of the pESI plasmid and serotype Infantis and will allow for the in vitro detection for epidemiological studies where whole-genome sequencing is not available.

McMillan, Elizabeth A. (ORCID:000000027503514X)↗
DOE OSTI2019

Analyzing the post-contrast attenuation of the esophageal wall on routine contrast-enhanced MDCT examination can improve the diagnostic accuracy in response evaluation of the squamous cell esophageal carcinoma to neoadjuvant chemoradiotherapy in comparison with the esophageal wall thickness

Purpose: To evaluate the accuracy of the multidetector computed tomography (MDCT) in the response evaluation of the esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT) by analyzing the thickness and post-contrast attenuation of the esophageal wall after the nCRT. Methods: Contrast-enhanced (CE)-MDCT examinations in portal venous phase of one hundred patients with locally advanced ESCC who received nCRT and underwent esophageal resection and histopathology assessment of tumor regression grade (TRG) were retrospectively analyzed by measuring the maximal thickness and mean density of the esophageal wall in the segment involved by tumor and visually searching for hyperdense foci within it. Diagnostic performance was evaluated using the ROC analysis. Results: Average attenuation of the esophageal wall had stronger diagnostic performance for predicting pathologic complete regression (pCR) (AUC = 0.994; p < 0.001) in relation to maximal esophageal wall thickness (AUC = 0.731; p < 0.001). Maximal esophageal wall thickness ≤ 9 mm and average attenuation of the esophageal wall ≤ 64 HU predicted pCR with the sensitivity, specificity, and overall accuracy of 62.5%, 77.9%, and 73%, and 96.9%, 98.5%, and 98%, respectively. Combination of both cutoff values enabled correct assessment of pCR with the 100% accuracy. Visual detection of the hyperdense focus within the esophageal wall predicted pCR with the sensitivity, specificity, and overall accuracy values of 100%, 94.1%, and 96%, respectively. Conclusion: Visual analysis and measurement of post-contrast attenuation of the esophageal wall after the nCRT can improve diagnostic accuracy of MDCT in the response evaluation of the ESCC to nCRT in comparison with measuring the esophageal wall thickness.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Catalytically inactive, purified RNase H1: A specific and sensitive probe for RNA–DNA hybrid imaging

R-loops are three-stranded nucleic acid structures with both physiological and pathological roles in cells. R-loop imaging generally relies on detection of the RNA–DNA hybrid component of these structures using the S9.6 antibody. We show that the use of this antibody for imaging can be problematic because it readily binds to double-stranded RNA (dsRNA) in vitro and in vivo, giving rise to nonspecific signal. In contrast, purified, catalytically inactive human RNase H1 tagged with GFP (GFP-dRNH1) is a more specific reagent for imaging RNA–DNA hybrids. GFP-dRNH1 binds strongly to RNA–DNA hybrids but not to dsRNA oligonucleotides in fixed human cells and is not susceptible to binding endogenous RNA. Furthermore, we demonstrate that purified GFP-dRNH1 can be applied to fixed cells to detect hybrids after their induction, thereby bypassing the need for cell line engineering. GFP-dRNH1 therefore promises to be a versatile tool for imaging and quantifying RNA–DNA hybrids under a wide range of conditions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Development of a Colorimetric Loop-Mediated Isothermal Amplification Assay for the Detection of Trypanosoma cruzi in Low-Resource Settings

Chagas disease is an inflammatory parasitic infection caused by Trypanosoma cruzi (T. cruzi). Early diagnosis is crucial in guiding treatment and slowing disease progression; however, current diagnostic methods have insufficient detection limits and often require skilled technicians. Molecular tests, especially isothermal nucleic acid assays, are advantageous due to their excellent sensitivity, specificity, speed, and simplicity. Here, we optimized a colorimetric loop-mediated isothermal amplification (LAMP) assay for T. cruzi. We can detect as few as 2 genomic copies/reaction using three different T. cruzi strains. We examined selectivity using other parasitic protozoans and successfully detected T. cruzi DNA extracted from parasites in human whole blood down to 1.2 parasite equivalents/reaction. We also performed a blinded study using canine blood samples and established a 100% sensitivity, specificity, and accuracy for the colorimetric LAMP assay. Finally, we used a heated 3D printer bed and an insulated thermos cup to demonstrate that the LAMP incubation step could be performed with accessible, low-cost materials. Altogether, we have developed a high-performing assay for T. cruzi with a simple colorimetric output that would be ideal for rapid, low-cost screening at the point of use.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Functional Gene Array-Based Ultrasensitive and Quantitative Detection of Microbial Populations in Complex Communities

ABSTRACT While functional gene arrays (FGAs) have greatly expanded our understanding of complex microbial systems, specificity, sensitivity, and quantitation challenges remain. We developed a new generation of FGA, GeoChip 5.0, using the Agilent platform. Two formats were created, a smaller format (GeoChip 5.0S), primarily covering carbon-, nitrogen-, sulfur-, and phosphorus-cycling genes and others providing ecological services, and a larger format (GeoChip 5.0M) containing the functional categories involved in biogeochemical cycling of C, N, S, and P and various metals, stress response, microbial defense, electron transport, plant growth promotion, virulence, gyrB , and fungus-, protozoan-, and virus-specific genes. GeoChip 5.0M contains 161,961 oligonucleotide probes covering >365,000 genes of 1,447 gene families from broad, functionally divergent taxonomic groups, including bacteria (2,721 genera), archaea (101 genera), fungi (297 genera), protists (219 genera), and viruses (167 genera), mainly phages. Computational and experimental evaluation indicated that designed probes were highly specific and could detect as little as 0.05 ng of pure culture DNAs within a background of 1 μg community DNA (equivalent to 0.005% of the population). Additionally, strong quantitative linear relationships were observed between signal intensity and amount of pure genomic (∼99% of probes detected; r > 0.9) or soil (∼97%; r > 0.9) DNAs. Application of the GeoChip to a contaminated groundwater microbial community indicated that environmental contaminants (primarily heavy metals) had significant impacts on the biodiversity of the communities. This is the most comprehensive FGA to date, capable of directly linking microbial genes/populations to ecosystem functions. IMPORTANCE The rapid development of metagenomic technologies, including microarrays, over the past decade has greatly expanded our understanding of complex microbial systems. However, because of the ever-expanding number of novel microbial sequences discovered each year, developing a microarray that is representative of real microbial communities, is specific and sensitive, and provides quantitative information remains a challenge. The newly developed GeoChip 5.0 is the most comprehensive microarray available to date for examining the functional capabilities of microbial communities important to biogeochemistry, ecology, environmental sciences, and human health. The GeoChip 5 is highly specific, sensitive, and quantitative based on both computational and experimental assays. Use of the array on a contaminated groundwater sample provided novel insights on the impacts of environmental contaminants on groundwater microbial communities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

SIPSim: A Modeling Toolkit to Predict Accuracy and Aid Design of DNA-SIP Experiments

DNA Stable isotope probing (DNA-SIP) is a powerful method that links identity to function within microbial communities. The combination of DNA-SIP with multiplexed high throughput DNA sequencing enables simultaneous mapping of in situ assimilation dynamics for thousands of microbial taxonomic units. Hence, high throughput sequencing enabled SIP has enormous potential to reveal patterns of carbon and nitrogen exchange within microbial food webs. There are several different methods for analyzing DNA-SIP data and despite the power of SIP experiments, it remains difficult to comprehensively evaluate method accuracy across a wide range of experimental parameters. We have developed a toolset (SIPSim) that simulates DNA-SIP data, and we use this toolset to systematically evaluate different methods for analyzing DNA-SIP data. Specifically, we employ SIPSim to evaluate the effects that key experimental parameters (e.g., level of isotopic enrichment, number of labeled taxa, relative abundance of labeled taxa, community richness, community evenness, and beta-diversity) have on the specificity, sensitivity, and balanced accuracy (defined as the product of specificity and sensitivity) of DNA-SIP analyses. Furthermore, SIPSim can predict analytical accuracy and power as a function of experimental design and community characteristics, and thus should be of great use in the design and interpretation of DNA-SIP experiments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Diagnostic performance of magnetic resonance to assess treatment response after neoadjuvant therapy in patients with locally advanced rectal cancer

Purpose: Our study aimed to evaluate the diagnostic performance of rectal magnetic resonance imaging (MRI) for local restaging in patients with non-metastatic locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) using surgical histopathology of total mesorectal excision as the reference standard. Methods: Ninety-five patients with LARC who underwent rectal MRI after CRT between January 2014 and December 2016 were included. Accuracy, sensitivity, specificity, positive, and negative predictive value for local staging regarding T-stage, N-stage, circumferential resection margin, and MRI tumor regression grade (ymriTRG) were calculated, and inter-test agreements were assessed. Results: 22/95 (23.2%) patients had radiological complete response (rCR), whereas 20/95 (21.1%) had pathological complete response (pCR). Among the patients with pCR, 11/20 (55%) had rCR. Fair agreement was demonstrated between ymriTRG and pathological TRG (ypTRG) (κ = 0.255). The sensitivity and specificity for detection of pCR were 61.1% (95% CI 35.7–82.7) and 89.6% (95% CI 80.6–95.4). For the detection of ypTRG grades 1 and 2, the corresponding values were 67.2% (95% CI 54.3–78.4) and 51.6 (95% CI 33.1–69.8). The accuracy of ymriTRG was 24.2% (95% CI 15.6–32.8). Inter-test agreement in TRG between MRI and pathology was overall fair (κ = 0.255) and slight (κ = 0.179), if TRG 1 + 2. Conclusion: Qualitative assessment on MRI for diagnosing pCR showed moderate sensitivity and high specificity, whereas the diagnosis of TRG had moderate sensitivity and low specificity with slight to fair inter-test agreement when compared with pathological specimens.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Comparative accuracy of qualitative and quantitative 18F-FDG PET/CT analysis in detection of lymph node metastasis from anal cancer

Purpose: To compare the diagnostic performance of qualitative and quantitative 18F-FDG PET/CT in detection of regional and distant lymph node metastasis in patients with anal cancer. Methods: Between 2004 and 2017, 28 patients with anal cancer who had staging PET/CT and pathological assessment of suspicious lymph nodes were included. For qualitative analysis, positive lymph nodes were defined as uptake visually higher than the liver reference uptake. For quantitative study, lymph nodes were contoured to determine maximum standard uptake value (SUV{sub max}) and metabolic tumor volume (MTV). Receiver operating characteristic (ROC) curves were plotted to extract the optimal cut-offs and area under the curve (AUC) of SUV{sub max}, lesion to background (L/B) ratio, short axis diameter (SAD), and MTV of lymph nodes. Histopathologic analysis was a reference standard. Results: A total of 28 lymph nodes (24 inguinal, 2 external iliac, 1 internal iliac, and 1 paraaortic nodes) in 28 patients on PET/CT were included. With the qualitative visual analysis, 19 patients were categorized as positive for nodal metastasis with sensitivity, specificity, and accuracy of 85%, 75%, and 82%. The optimal SUV{sub max} and L/B ratio cut-offs were 2.6 and 1.0 with both sensitivity and specificity of 95% and 75% (AUC of SUV{sub max} = 0.893, AUC of L/B ratio = 0.912). Using the best cut-off of 1.6 cm for SAD and 3.65 cm{sup 3} for MTV, both sensitivity and specificity were 80% and 100% (AUC of SAD = 0.950, AUC of MTV = 0.931). Conclusions: SUV{sub max} optimization may be helpful in enhancing the diagnostic accuracy of 18F-FDG PET/CT in nodal staging patients with anal cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗