Search NASA⌕ Search

SEARCH · Search NASA

Results for “LABELLING”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13

D-Band EPR and ENDOR Spectroscopy of 15 N-Labeled Photosystem I

For billions of years, nature has optimized the photosynthetic machinery that converts light energy into chemical energy. Key primary reactions of photosynthesis occur in large membrane protein-cofactor complexes. The light-induced sequential electron transfer reactions occur through a chain of donor/acceptor cofactors embedded in the protein matrix resulting in a long-lived transmembrane charge-separated state. EPR is the method of choice to study electron transfer and the interaction of protein environment with redox-active cofactors. However, the spectra of organic cofactor radicals typically are not fully resolved and severely overlap at conventional X-band EPR. Even at Q-band EPR, this overlap is present and often a serious problem. As a result, there is a large variation of the reported EPR data and limited understanding of electronic structures of several redox-active cofactors. These serious problems can often be overcome by the excellent spectral resolution provided by high-frequency EPR (HF EPR). In this work, we study the electronic structure of the primary electron donor P 700 and the secondary electron acceptor A 1 of Photosystem I (PSI) using 130 GHz (D-band) EPR and Electron-Nuclear-Double-Resonance (ENDOR) spectroscopy. PSI was isotopically labeled with 15 N (I = $\frac{1/2}$) to avoid quadrupolar interactions in the most abundant nitrogen isotope 14 N (I = 1) and simplify the ENDOR spectra. ENDOR spectroscopy is central for determining the hyperfine coupling of nitrogen atoms of the two chlorophyll molecules comprising oxidized P 700 and the involvement of protein nitrogen atoms with reduced A 1 . While HF ENDOR of A 1 - allows identification of two nitrogen atoms, HF ENDOR of P 700 + still does not permit unique assignment of the recorded hyperfine couplings.

15N↗

Lignin-based carbon quantum dots with high fluorescence performance prepared by supercritical catalysis and solvothermal treatment for tumor-targeted labeling

The poor fluorescence performance of lignin-based carbon quantum dots (L-CQDs) prepared using the bottom-up method has hindered their development. Here, in this study, a two-step strategy was proposed to efficiently enhance the fluorescence properties of L-CQDs. Lignin was first cracked using an ethanol supercritical/noble metal catalyst; then, the L-CQDs were prepared with the cracked lignin fragments as carbon precursors without adding any modified reagents. Compared with the OL-CQDs prepared by the traditional one-pot hydrothermal method, the L-CQDs-1 prepared from CL-1 containing much low molecular weight compounds, and have photoluminescence (increased from 63 to 975) and excellent up-conversion photoluminescence (enhanced by 16.3 to 963), which significantly enhanced by about 15 times and 60 times, respectively. They can emit bright blue fluorescence under both ultraviolet and near-infrared light irradiation owing to a large amount of surface defects caused by the rich compound composition. When L-CQDs-1 were combined with, and quenched by folic acid (FA), the prepared FA@L-CQDs-1 show the ability to target and label tumor cells. This study opens new avenues for the preparation of L-CQDs with high fluorescence performance using lignocellulosic material without heteroatom additives.

59 BASIC BIOLOGICAL SCIENCES↗

Label-free detection of Herceptin ® using suspended silicon microring resonators

In this paper, highly sensitive detection of heat denatured Herceptin ® (trastuzumab), an important monoclonal antibody used in breast cancer therapeutics, is demonstrated using transverse magnetic (TM) mode suspended microring resonators (MRRs). The suspended MRRs are surface functionalized with a single chain fragment variable (scFv) recombinant antibody molecule (designated 2B4) that enables selective capture of denatured Herceptin molecules. Interaction between guided modes in suspended MRRs and Herceptin molecules captured on the surfaces of the suspended MRRs enable straightforward optical detection and quantification of the bound Herceptin molecules. Clinically relevant Herceptin detection at a concentration of 100 nM is demonstrated and negligible signal was obtained from the sensor when exposed to Avastin ® (bevacizumab), a negative control human therapeutic monoclonal antibody. Importantly, at least a 2-fold enhanced detection sensitivity is obtained by suspending the microring (MRR) over the underlying substrate, effectively increasing the sensing surface area. Experimental results are supported by three-dimensional finite-difference time-domain simulations and optical mode analysis. Finally, the use of a label-free silicon photonic platform for high sensitivity molecular detection is compatible with high-throughput, low-cost diagnostics employing on-chip sensor arrays.

47 OTHER INSTRUMENTATION↗

Coupling Microdroplet-Based Sample Preparation, Multiplexed Isobaric Labeling, and Nanoflow Peptide Fractionation for Deep Proteome Profiling of the Tissue Microenvironment

There is increasing interest in developing in-depth proteomic approaches for mapping tissue heterogeneity in a cell-type-specific manner to better understand and predict the function of complex biological systems such as human organs. Existing spatially resolved proteomics technologies cannot provide deep proteome coverage due to limited sensitivity and poor sample recovery. Herein, we seamlessly combined laser capture microdissection with a low-volume sample processing technology that includes a microfluidic device named microPOTS (microdroplet processing in one pot for trace samples), multiplexed isobaric labeling, and a nanoflow peptide fractionation approach. The integrated workflow allowed us to maximize proteome coverage of laser-isolated tissue samples containing nanogram levels of proteins. We demonstrated that the deep spatial proteomics platform can quantify more than 5000 unique proteins from a small-sized human pancreatic tissue pixel (∼60,000 μm2) and differentiate unique protein abundance patterns in pancreas. Furthermore, the use of the microPOTS chip eliminated the requirement for advanced microfabrication capabilities and specialized nanoliter liquid handling equipment, making it more accessible to proteomic laboratories.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

99m Tc-, 90 Y-, and 177 Lu-Labeled Iron Oxide Nanoflowers Designed for Potential Use in Dual Magnetic Hyperthermia/Radionuclide Cancer Therapy and Diagnosis

Development of a complex based on iron oxide nanoparticles (IONPs) for diagnosis and dual magnetic hyperthermia/radionuclide cancer therapy accomplishing high yields of radiolabeling and great magnetic heat induction is still a challenge. We report here the synthesis of citric acid, poly(acrylic acid) (PAA) and poly(ethylene glycol) coated IONPs and their labeling with three radionuclides, namely, technetium (99mTc), yttrium (90Y), and lutetium (177Lu), aiming at potential use in cancer diagnosis and therapy. Polyol-synthesized IONPs are a flowerlike structure with 13.5 nm spherically shaped cores and 24.8 nm diameter. PAA-coated nanoparticles (PAA@IONP) showed the best characteristics such as easy radiolabeling with very high yields (>97.5%) with all three radionuclides, and excellent in vitro stabilities with less than 10% of radionuclides detaching after 24 h. Heating ability of PAA@IONP in an alternating external magnetic field showed intrinsic loss power value of 7.3 nH m2/kg, which is one of higher reported values. Additionally, PAA@IONP itself presented no significant cytotoxicity to the CT-26 cancer cells, reaching IC50 at 60 μg/mL. However, under the external magnetic field, they show hyperthermia-mediated cells killing, which correlated with the magnetic field strength and time of exposure. Since PAA@IONP are easy to prepare, biocompatible, and with excellent magnetic heat induction, these nanoparticles radiolabeled with high-energy beta emitters 90Y and 177Lu have valuable potential as agent for dual magnetic hyperthermia/radionuclide therapy, while radiolabeled with 99mTc could be used in diagnostic imaging. Copyright © 2019 American Chemical Society.

60 APPLIED LIFE SCIENCES↗

Label-free functional analysis of root-associated microbes with dynamic quantitative oblique back-illumination microscopy

The increasing global demand for food, coupled with concerns about the environmental impact of synthetic fertilizers, underscores the urgency of developing sustainable agricultural practices. Nitrogen-fixing bacteria, known as diazotrophs, offer a potential solution by converting atmospheric nitrogen into bioavailable forms, reducing the reliance on synthetic fertilizers. However, a deeper understanding of their interactions with plants and other microbes is needed. In this study, we introduce a recently developed label-free 3D quantitative phase imaging technology called dynamic quantitative oblique back-illumination microscopy (DqOBM) to assess the functional dynamic activity of diazotrophs in vitro and in situ. Our experiments involved three different diazotrophs (Sinorhizobium meliloti, Azotobacter vinelandii, and Rahnella aquatilis) cultured on media with amendments of carbon and nitrogen sources. Over 5 days, we observed increased dynamics in nutrient-amended media. These results suggest that the observed bacterial dynamics correlate with their metabolic activity. Furthermore, we applied qOBM to visualize microbial dynamics within the root cap and elongation zone of Arabidopsis thaliana primary roots. This allowed us to identify distinct areas of microbial infiltration in plant roots without the need for fluorescent markers. Our findings demonstrate that DqOBM can effectively characterize microbial dynamics and provide insights into plant-microbe interactions in situ, offering a valuable tool for advancing our understanding of sustainable agriculture.

59 BASIC BIOLOGICAL SCIENCES↗

Is the Kok effect a respiratory phenomenon? Metabolic insight using 13 C labeling in Helianthus annuus leaves

The Kok effect is a well-known phenomenon in which the quantum yield of photosynthesis changes abruptly at low light. This effect has often been interpreted as a shift in leaf respiratory metabolism and thus used widely to measure day respiration. However, there is still no formal evidence that the Kok effect has a respiratory origin. Here, both gas exchange and isotopic labeling were carried out on sunflower leaves, using glucose that was 13 C-enriched at specific C-atom positions. Position-specific decarboxylation measurements and NMR analysis of metabolites were used to trace the fate of C-atoms in metabolism. Decarboxylation rates were significant at low light (including above the Kok break point) and increased with decreasing irradiance below 100 µmol photons m –2 s –1 . The variation in several metabolite pools such as malate, fumarate or citrate, and flux calculations suggest the involvement of several decarboxylating pathways in the Kok effect, including the malic enzyme. Our results show that day respiratory CO 2 evolution plays an important role in the Kok effect. Furthermore, the increase in the apparent quantum yield of photosynthesis below the Kok break point is also probably related to malate metabolism, which participates in maintaining photosynthetic linear electron flow.

54 ENVIRONMENTAL SCIENCES↗

From Escherichia coli mutant 13 C labeling data to a core kinetic model: A kinetic model parameterization pipeline

Kinetic models of metabolic networks offer the promise of quantitative phenotype prediction. The mechanistic characterization of enzyme catalyzed reactions allows for tracing the effect of perturbations in metabolite concentrations and reaction fluxes in response to genetic and environmental perturbation that are beyond the scope of stoichiometric models. In this study, we develop a two-step computational pipeline for the rapid parameterization of kinetic models of metabolic networks using a curated metabolic model and available 13 C-labeling distributions under multiple genetic and environmental perturbations. The first step involves the elucidation of all intracellular fluxes in a core model of E. coli containing 74 reactions and 61 metabolites using 13 C-Metabolic Flux Analysis ( 13 C-MFA). Here, fluxes corresponding to the mid-exponential growth phase are elucidated for seven single gene deletion mutants from upper glycolysis, pentose phosphate pathway and the Entner-Doudoroff pathway. The computed flux ranges are then used to parameterize the same (i.e., k-ecoli74) core kinetic model for E. coli with 55 substrate-level regulations using the newly developed K-FIT parameterization algorithm. The K-FIT algorithm employs a combination of equation decomposition and iterative solution techniques to evaluate steady-state fluxes in response to genetic perturbations. k-ecoli74 predicted 86% of flux values for strains used during fitting within a single standard deviation of 13 C-MFA estimated values. By performing both tasks using the same network, errors associated with lack of congruity between the two networks are avoided, allowing for seamless integration of data with model building. Product yield predictions and comparison with previously developed kinetic models indicate shifts in flux ranges and the presence or absence of mutant strains delivering flux towards pathways of interest from training data significantly impact predictive capabilities. Using this workflow, the impact of completeness of fluxomic datasets and the importance of specific genetic perturbations on uncertainties in kinetic parameter estimation are evaluated.

59 BASIC BIOLOGICAL SCIENCES↗

Interrogating Plant-Microbe Interactions with Chemical Tools: Click Chemistry Reagents for Metabolic Labeling and Activity-Based Probes

Continued expansion of the chemical biology toolbox presents many new and diverse opportunities to interrogate the fundamental molecular mechanisms driving complex plant–microbe interactions. This review will examine metabolic labeling with click chemistry reagents and activity-based probes for investigating the impacts of plant-associated microbes on plant growth, metabolism, and immune responses. While the majority of the studies reviewed here used chemical biology approaches to examine the effects of pathogens on plants, chemical biology will also be invaluable in future efforts to investigate mutualistic associations between beneficial microbes and their plant hosts.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Covalent labeling of the Arabidopsis plasma membrane H + ‐ ATPase reveals 3D conformational changes involving the C‐terminal regulatory domain

The plasma membrane proton pump is the primary energy transducing, electrogenic ion pump of the plasma membrane in plants and fungi. Compared to its fungal counterpart, the plant plasma membrane proton pump's regulatory C‐terminal domain (CTD) contains an additional regulatory segment that links multiple sensory pathways regulating plant cell length through phosphorylation and recruitment of regulatory 14‐3‐3 proteins. However, a complete structural model of a plant proton pump is lacking. Here, we performed covalent labeling with mass spectrometric analysis (CL‐MS) on the Arabidopsis pump AHA2 to identify potential interactions between the CTD and the catalytic domains. Our results suggest that autoinhibition in the plant enzyme is much more structurally complex than in the fungal enzyme.

Blackburn, Matthew R. [Department of Biochemistry ↗

Synergistic Integration of Chemo-Resistive and SERS Sensing for Label-Free Multiplex Gas Detection

Practical sensing applications such as real-time safety alerts and clinical diagnoses require sensor devices to differentiate between various target molecules with high sensitivity and selectivity, yet conventional devices such as oxide-based chemo-resistive sensors and metal-based surface-enhanced Raman spectroscopy (SERS) sensors usually do not satisfy such requirements. In this report a label-free, chemo-resistive/SERS multimodal sensor based on a systematically assembled 3D cross-point multifunctional nanoarchitecture (3D-CMA), which has unusually strong enhancements in both “chemo-resistive” and “SERS” sensing characteristics is introduced. 3D-CMA combines several sensing mechanisms and sensing elements via 3D integration of semiconducting SnO 2 nanowire frameworks and dual-functioning Au metallic nanoparticles. It is shown that the multimodal sensor can successfully estimate mixed-gas compositions selectively and quantitatively at the sub-100 ppm level, even for mixtures of gaseous aromatic compounds (nitrobenzene and toluene) with very similar molecular structures. This is enabled by combined chemo-resistive and SERS multimodal sensing providing complementary information.

36 MATERIALS SCIENCE↗

Surface Functionalization of Black Phosphorus with Nitrenes: Identification of P=N Bonds by Using Isotopic Labeling

Abstract Surface functionalization of two‐dimensional crystals is a key path to tuning their intrinsic physical and chemical properties. However, synthetic protocols and experimental strategies to directly probe chemical bonding in modified surfaces are scarce. Introduced herein is a mild, surface‐specific protocol for the surface functionalization of few‐layer black phosphorus nanosheets using a family of photolytically generated nitrenes (RN) from the corresponding azides. By embedding spectroscopic tags in the organic backbone, a multitude of characterization techniques are employed to investigate in detail the chemical structure of the modified nanosheets, including vibrational, X‐ray photoelectron, solid state 31 P NMR, and UV‐vis spectroscopy. To directly probe the functional groups introduced on the surface, R fragments were selected such that in conjunction with vibrational spectroscopy, 15 N‐labeling experiments, and DFT methods, diagnostic P=N vibrational modes indicative of iminophosphorane units on the nanosheet surface could be conclusively identified.

Walz Mitra, Kendahl L.↗

Label‐free Voltammetric Detection of Products of Terminal Deoxynucleotidyl Transferase Tailing Reaction

Abstract A label‐free approach that takes advantage of intrinsic electrochemical activity of nucleobases has been applied to study the products of terminal deoxynucleotidyl transferase (TdT) tailing reaction. DNA homooligonucleotides A 30 , C 30 and T 30 were used as primers for the tailing reaction to which a dNTP – or a mixture of dNTPs – and TdT were added to form the tails. Electrochemical detection enabled study of the tailing reaction products created by various combinations of primers and dNTPs, with pyrolytic graphite electrode (PGE) being suitable for remarkably precise analysis of the length of tailing reaction products. Furthermore, the hanging mercury drop electrode (HMDE) was able to reveal formation of various DNA structures, such as DNA hairpins and G‐quadruplexes, which influence the behavior of DNA molecules at the negatively charged surface of HMDE. Thus, the described approach proves to be an excellent tool for studying the TdT tailing reactions and for exploring how various DNA structures affect both the tailing reactions and electrochemical behavior of DNA oligonucleotides at electrode surfaces.

Hermanová, Monika↗

One-Pot Hydrothermal Synthesis of Elements (B, N, P)-Doped Fluorescent Carbon Dots for Cell Labelling, Differentiation and Outgrowth of Neuronal Cells

The use of the chemically modified one-step facile hydrothermal process to develop Boron (B), Nitrogen (N), and Phosphorous (P) doped carbon dots (E@CDs) is reported on in this work. The chemical characterization of the E@CDs was systematically studied by several analytical techniques that confer doping of elements by known characteristics. The obtained E@CDs had observed very homogeneous size distribution and displayed excitation dependent fluorescence properties, and high quantum yield (QY) was measured in case of B and N doping. Excellent cell viability and good cellular uptake was observed for all E@CDs. Lastly, E@CDs were compared with pristine CDs on their effect on cell labelling, neural differentiation process and outgrowth of neurite network. By manipulating the doping of CDs, we can control the branching pattern and outgrowth of neuronal developments. The E@CDs are capable due to their photostability biocompatibility, and possible selective affinity towards nanomedicine applications.

36 MATERIALS SCIENCE↗

Robust surfactant-assisted one-pot sample preparation for label-free single-cell and nanoscale proteomics

With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk cells. However, such bulk measurement obscures cell to cell heterogeneity, precluding proteome profiling of single cells and small numbers of cells of interest. To address this issue, in recent 5 years there are a surge of small sample preparation methods developed for robust effective collection and processing of single cells and small numbers of cells for in-depth MS-based proteome profiling. Based on their broad accessibility, they can be categorized into two types: specific device- and standard PCR tube- or multi-well plate-based methods. Herein we describe the detailed protocol of our recently developed, easily adoptable, Surfactant-assisted One-Pot (SOP) sample preparation coupled with MS method termed SOP-MS for label-free single-cell and nanoscale proteomics. SOP-MS capitalizes on the combination of a MS-compatible surfactant, DDM (n-Dodecyl-ß-D-maltoside), and standard low-bind PCR tube or multi-well plate for ‘all-in-one’ one-pot sample preparation without sample transfer. With its robust and convenient features, SOP-MS can be readily implemented in any MS laboratory for single-cell and nanoscale proteomics. With further improvements in MS detection sensitivity and sample throughput, we believe that SOP-MS could open an avenue for single-cell proteomics with broad applicability in the biological and biomedical research.

Single-cell proteomics, nanoscale proteomics, SOP-↗

Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers

Background: Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed. Methods: Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others. Results: Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group. Conclusion: Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

ProvSec: Open Cybersecurity System Provenance Analysis Benchmark Dataset with Labels

System provenance forensic analysis has been studied by a large body of research work. This area needs fine granularity data such as system calls along with event fields to track the dependencies of events. While prior work on security datasets has been proposed, we found a useful dataset of realistic attacks and details that are needed for high-quality provenance tracking is lacking. We created a new dataset of eleven vulnerable cases for system forensic analysis. It includes the full details of system calls including syscall parameters. Realistic attack scenarios with real software vulnerabilities and exploits are used. For each case, we created two sets of benign and adversary scenarios which are manually labeled for supervised machine-learning analysis. In addition, we present an algorithm to improve the data quality in the system provenance forensic analysis. We demonstrate the details of the dataset events and dependency analysis of our dataset cases.

97 MATHEMATICS AND COMPUTING↗

Preliminary investigation of 48 V-labeled VO(acac) 2 for cancer imaging: An initial proof-of-concept study

In this preliminary study, a procedure for synthesizing novel PET radiotracer vanadium-48-labeled-vanadyl acetylacetonate was developed, including radioisotope production via cyclotron, separation of 48 V, chelation as 48 VO(acac) 2 , and assessment through in vitro cellular studies. We employed the beam-stop setup in a cyclotron as the target holder to irradiate titanium foils in the reaction of nat Ti (p,n) 48 V. The radioisotope production rate was 4.84 ± 0.67 μCi/μA-h. Overall radiochemical yield was 12.86 ± 0.51% with gamma-ray spectroscopy showing no detectable contaminant peaks. HPLC of 48 VO(acac) 2 showed a retention time (1:48) corresponding closely to that (1:50) of commercial VO(acac) 2 , verifying the successful synthesis of 8VO(acac) 2 . In vitro cellular studies demonstrated radiotracer uptake and saturation around 0.48 nM. These studies pave the way for improving methodologies and in vivo experiments, including imaging studies, in future investigations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗