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Results for “Function analysis”

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At least 919 records · Page 51
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Use of virus‐induced gene silencing to characterize genes involved in modulating hypersensitive cell death in maize

Abstract Plant disease resistance proteins (R‐proteins) detect specific pathogen‐derived molecules, triggering a defence response often including a rapid localized cell death at the point of pathogen penetration called the hypersensitive response (HR). The maize Rp1‐D21 gene encodes a protein that triggers a spontaneous HR causing spots on leaves in the absence of any pathogen. Previously, we used fine mapping and functional analysis in a Nicotiana benthamiana transient expression system to identify and characterize a number of genes associated with variation in Rp1‐D21 ‐induced HR. Here we describe a system for characterizing genes mediating HR, using virus‐induced gene silencing (VIGS) in a maize line carrying Rp1‐D21 . We assess the roles of 12 candidate genes. Three of these genes, SGT1 , RAR1 , and HSP90 , are required for HR induced by a number of R‐proteins across several plant–pathogen systems. We confirmed that maize HSP90 was required for full Rp1‐D21 ‐induced HR. However, suppression of SGT1 expression unexpectedly increased the severity of Rp1‐D21 ‐induced HR while suppression of RAR1 expression had no measurable effect. We confirmed the effects on HR of two genes we had previously validated in the N. benthamiana system, hydroxycinnamoyltransferase and caffeoyl CoA O‐methyltransferase . We further showed the suppression the expression of two previously uncharacterized, candidate genes, IQ calmodulin binding protein ( IQM3 ) and vacuolar protein sorting protein 37 , suppressed Rp1‐D21 ‐induced HR. This approach is an efficient way to characterize the roles of genes modulating the hypersensitive defence response and other dominant lesion phenotypes in maize.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

SU-D-BRD-04: A Logical Organizational Approach to Clinical Information Management

Purpose: To develop a clinical information management system (CIMS) that collects, organizes physician inputs logically and supports analysis functionality. Methods: In a conventional electronic medical record system (EMR), the document manager component stores data in a pool of standalone .docx or .pdf files. The lack of a content-based logical organization makes cross-checking, reference or automatic inheritance of information challenging. We have developed an information-oriented clinical record system that addresses this shortcoming. In CIMS, a parent library predefines a set of available questions along with the data types of their expected answers. The creation of a questionnaire template is achieved by selecting questions from this parent library to form a virtual group. Instances of the same data field in different documents are linked by their question identifier. This design allows for flexible data sharing and inheritance among various forms using a longitudinal lineage of data indexed according to the modification time stamps of the documents. CIMS is designed with a web portal to facilitate querying, data entry and modification, aggregate report generation, and data adjudication. The current implementation addresses diagnostic data, medical history, vital signs, and various quantities in consult note and treatment summaries. Results: CIMS is currently storing treatment summary information of over 1,000 patients who have received treatment at UCLA Radiation Oncology between March 1, 2013 and January 31, 2014. We are in the process of incorporating a DICOM-RT dosimetry parser and patient reporting applications into CIMS, as well as continuing to define document templates to support additional forms. Conclusion: We are able to devise an alternative storage paradigm which results in an improvement in the accuracy and organizational structure of clinical information.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound

Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 × 144 × 135 mm{sup 3} FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled “truth” below 0.35 °C. Conclusions: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations.

42 ENGINEERING↗
DOE OSTI2016

SU-F-T-568: QA of a Multi-Target Multi-Dose VMAT SRS

Purpose: To, experimentally, corroborated the prescribed doses utilizing dosimeters (e.g. films and TLDs) that can provide high spatial resolution, allow dose measurement of multiple targets at once, and provide accurate dosimetric results. Methods: A single-isocenter 6FFF SRS VMAT plan consisting of one 358° arc at 0° couch angle and four 179° arcs at 30°, 60°, 330° and 300° couch angles respectively, was generated in ECLIPSE v.11 using a Rando-Alderson anthropomorphic head phantom CT study. This plan was a reproduction of a clinical plan generated for a stage-IV melanoma patient diagnosed with 19 intracranial lesions. The phantom was loaded with axially mounted (between phantom slabs) Gafchromic EBT3 film and TLDs strategically positioned within various target volumes. Film and TLDS were calibrated according to established protocols. Target prescription doses were 16 Gy (3cc≤, 3 lesions), 18 Gy (∼1–3cc, 10 lesions) and 20 Gy (≤1cc, 6 lesions). Phantom setup was verified through CBCT imaging prior to irradiation. Gafchromic films were scanned in transmission mode and TLDs were read, respectively, ∼24 hrs after irradiation. Results: Dose calibrated Gafchromic film data were compared to the ECLIPSE calculated data using a 3% / 3mm gamma function analysis. Results for the gamma values were 96–99% in agreement with the calculated data and with 84–90% of the film pixels within the 3% dose difference. TLD data showed a dose difference of 0.4–8% while the film data for those same locations yielded a difference of 0.4–4%. It was observed that the highest dose discrepancies correlated with the location of the small volume targets. Conclusion: Overall this study corroborated that a VMAT SRS treatment, employing various treatment table rotations and arcs, to multiple intracranial lesions with multiple dose prescriptions can be delivered accurately with the existing radiotherapy technology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

WE-AB-202-04: Statistical Evaluation of Lung Function Using 4DCT Ventilation Imaging: Proton Therapy VS IMRT

Purpose: Variation in function of different lung regions has been ignored so far for conventional lung cancer treatment planning, which may lead to higher risk of radiation induced lung disease. 4DCT based lung ventilation imaging provides a novel yet convenient approach for lung functional imaging as 4DCT is taken as routine for lung cancer treatment. Our work aims to evaluate the impact of accounting for spatial heterogeneity in lung function using 4DCT based lung ventilation imaging for proton and IMRT plans. Methods: Six patients with advanced stage lung cancer of various tumor locations were retrospectively evaluated for the study. Proton and IMRT plans were designed following identical planning objective and constrains for each patient. Ventilation images were calculated from patients’ 4DCT using deformable image registration implemented by Velocity AI software based on Jacobian-metrics. Lung was delineated into two function level regions based on ventilation (low and high functional area). High functional region was defined as lung ventilation greater than 30%. Dose distribution and statistics in different lung function area was calculated for patients. Results: Variation in dosimetric statistics of different function lung region was observed between proton and IMRT plans. In all proton plans, high function lung regions receive lower maximum dose (100.2%–108.9%), compared with IMRT plans (106.4%–119.7%). Interestingly, three out of six proton plans gave higher mean dose by up to 2.2% than IMRT to high function lung region. Lower mean dose (lower by up to 14.1%) and maximum dose (lower by up to 9%) were observed in low function lung for proton plans. Conclusion: A systematic approach was developed to generate function lung ventilation imaging and use it to evaluate plans. This method hold great promise in function analysis of lung during planning. We are currently studying more subjects to evaluate this tool.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Nannochloropsis oceanica IMET1 and its bacterial symbionts for carbon capture, utilization, and storage: biomass and calcium carbonate production under high pH and high alkalinity

ABSTRACT To combat the increasing levels of carbon dioxide (CO 2 ) released from the combustion of fossil fuels, microalgae have emerged as a promising strategy for biological carbon capture, utilization, and storage. This study used a marine microalgal strain, Nannochloropsis oceanica IMET1, which thrives in high CO 2 concentrations. A high-pH, high-alkalinity culture was designed for CO 2 capture through algal biomass production as well as permanent sequestration through calcium carbonate (CaCO 3 ) precipitation. This was accomplished by timed pH elevation and the addition of sodium bicarbonate to cultures of N. oceanica grown at lab scale (1 L) and pilot scale (500 L) with 10% and 5% CO 2 , respectively. Our data showed that 0.02 M NaHCO 3 promoted algal growth and that sparging cultures with ambient air after 12 days raised pH and created favorable CaCO 3 formation conditions. At the 1 L scale, we reached 1.52 g L −1 biomass after 12 days and an extra 9.3% CO 2 was captured in the form of CaCO 3 precipitates. At the 500 L pilot scale, an extra 60% CO 2 was captured (Day 40) with a maximum CO 2 capture rate of 63.2 g m −2 day −1 (Day 35). Bacterial communities associated with the microalgae were dominated by two novel Patescibacteria. Functional analysis revealed that genes for several plant growth-promotion traits (PGPTs) were enriched within this group. The microalgal-bacterial coculture system offers advantages for enhanced carbon mitigation through biomass production and simultaneous precipitation of recalcitrant CaCO 3 for long-term CO 2 storage. IMPORTANCE Capturing carbon dioxide (CO 2 ) released from fossil fuel combustion is of the utmost importance as the impacts of climate change continue to worsen. Microalgae can remove CO 2 through their natural photosynthetic pathways and are additionally able to convert CO 2 into a stable, recalcitrant form as calcium carbonate (CaCO 3 ). We demonstrate that microalgae-based carbon capture systems can be greatly improved with high pH and high alkalinity by providing optimal conditions for carbonate precipitation. Our results with the microalga, Nannochloropsis oceanica strain IMET1, show an extra 9.3% CO 2 captured as CaCO 3 at the 1 L scale and an extra 60% CO 2 captured at the 500 L (pilot) scale. Our optimized system provides a novel approach to capture CO 2 through two mechanisms: (i) as organic carbon within microalgal biomass and (ii) as inorganic carbon stored permanently in the form of CaCO 3.

20 FOSSIL-FUELED POWER PLANTS↗
DOE OSTI2015

Genetic Background Modulates lncRNA-Coordinated Tissue Response to Low Dose Ionizing Radiation

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed after LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2021

Dynamical Components Analysis (DCA) v1.0.0

Dynamical Components Analysis is a Python implementation of the method described in "Unsupervised discovery of temporal structure in noisy data with dynamical components analysis". It implements the method as well as related data analysis functions.

Livezey, Jesse↗
DOE OSTI2021

Dynamical Components Analysis (DCA) v1.0.0

Dynamical Components Analysis is a Python implementation of the method described in "Unsupervised discovery of temporal structure in noisy data with dynamical components analysis". It implements the method as well as related data analysis functions.

Livezey, Jesse↗
DOE OSTI2026

EFBMC

SAND2026-23986O EFBMC performs elastic Bayesian model calibration by applying Bayesian statistics and functional analysis. The software provides Python, R, and MATLAB scripts that enable users to calibrate models. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Tucker, J. Derek [Sandia National Lab. (SNL-CA), L↗
DOE OSTI2016

Impacts of the Pacific–Japan and Circumglobal Teleconnection Patterns on the Interdecadal Variability of the East Asian Summer Monsoon

Based on the Twentieth Century Reanalysis (20CR) dataset, the dominant modes of interdecadal variability of the East Asian summer monsoon (EASM) are investigated through a multivariate empirical orthogonal function analysis (MV-EOF). The first mode (EA1) is characterized by an anomalous cyclone centered over Taiwan and an anomalous anticyclone centered over the Bohai Sea. These phenomena are part of the meridional wave–like teleconnection pattern propagating poleward from the southern tropical western North Pacific (WNP), referred to as the interdecadal Pacific–Japan (PJ) pattern. The interdecadal PJ pattern is driven by negative anomalous convective heating over the southern tropical WNP, which is associated with the interdecadal Pacific oscillation (IPO) and the interdecadal Indian Ocean basin mode (IOBM). The amplitude of the EA1 and its contribution to the total variance of the EASM decrease remarkably after the 1960s. The second MV-EOF mode (EA2) is characterized by cyclone anomalies extending from northeastern China to Japan, which are part of a circumglobal wave train. Given the spatial scale of the wave train in the zonal direction (wavenumber 5), as well as the fact that it possesses barotropic structures and propagates along the Northern Hemispheric jet stream, it is referred to herein as the interdecadal circumglobal teleconnection (CGT) pattern. The interdecadal CGT pattern is associated with the forcing from the Atlantic multidecadal oscillation (AMO). Though the interdecadal PJ and CGT patterns are derived from the 20CR dataset, they are carefully verified through comparisons with various observational and reanalysis datasets from different perspectives.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

RECK is not an independent prognostic marker for breast cancer

Background The REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear. Methods The RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated. Results Higher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables. Conclusions Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Exploring soybean metabolic pathways based on probabilistic graphical model and knowledge-based methods

Soybean (Glycine max) is a major source of vegetable oil and protein for both animal and human consumption. The completion of soybean genome sequence led to a number of transcriptomic studies (RNA-seq), which provide a resource for gene discovery and functional analysis. Several data-driven (e.g., based on gene expression data) and knowledge-based (e.g., predictions of molecular interactions) methods have been proposed and implemented. In order to better understand gene relationships and protein interactions, we applied probabilistic graphical methods, based on Bayesian network and knowledgebase constraints using gene expression data to reconstruct soybean metabolic pathways. The results show that this method can predict new relationships between genes, improving on traditional reference pathway maps.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

Structural and Biochemical Characterization of the Human Cyclophilin Family of Peptidyl-Prolyl Isomerases

Peptidyl-prolyl isomerases catalyze the conversion between cis and trans isomers of proline. The cyclophilin family of peptidyl-prolyl isomerases is well known for being the target of the immunosuppressive drug cyclosporin, used to combat organ transplant rejection. There is great interest in both the substrate specificity of these enzymes and the design of isoform-selective ligands for them. However, the dearth of available data for individual family members inhibits attempts to design drug specificity; additionally, in order to define physiological functions for the cyclophilins, definitive isoform characterization is required. In the current study, enzymatic activity was assayed for 15 of the 17 human cyclophilin isomerase domains, and binding to the cyclosporin scaffold was tested. In order to rationalize the observed isoform diversity, the high-resolution crystallographic structures of seven cyclophilin domains were determined. These models, combined with seven previously solved cyclophilin isoforms, provide the basis for a family-wide structure:function analysis. Detailed structural analysis of the human cyclophilin isomerase explains why cyclophilin activity against short peptides is correlated with an ability to ligate cyclosporin and why certain isoforms are not competent for either activity. In addition, we find that regions of the isomerase domain outside the proline-binding surface impart isoform specificity for both in vivo substrates and drug design. We hypothesize that there is a well-defined molecular surface corresponding to the substrate-binding S2 position that is a site of diversity in the cyclophilin family. Computational simulations of substrate binding in this region support our observations. Our data indicate that unique isoform determinants exist that may be exploited for development of selective ligands and suggest that the currently available small-molecule and peptide-based ligands for this class of enzyme are insufficient for isoform specificity.

59 BASIC BIOLOGICAL SCIENCES↗