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At least 55 records · Page 3

TexAT detector upgrade for 14 O($α$, $p$) 17 F cross section measurement

A direct cross-section measurement of the 14 O($α$, $p$) 17 F reaction is important to understand the light curves of x-ray bursts. The measurement will be performed using the Texas Active Target TPC version 2 (TexAT_v2). The TexAT_v2 aims at measuring lower energy protons from the reaction than the original TexAT. Newly developed silicon and CsI(Tl) detector arrays are added at the left, right and bottom of a modified field cage to increase its detection efficiency. Furthermore, this paper describes the overall specifications and two commissioning experiments performed at Texas A&M University.

14O(α, p)17F↗

Beta-delayed charged-particle spectroscopy using TexAT

β-delayed charged-particle emission is a sensitive probe of three-body decays in light nuclei. Time Projection Chambers (TPCs) offer a significant advantage over traditional charged-particle spectroscopy techniques due to a low-energy threshold and a high-geometric efficiency (≈ 4π) which are essential for use with radioactive ion beams where the beam intensities are limited. The technique for high-sensitivity spectroscopy of β-delayed charged-particle emission is shown to be possible using the Texas Active Target (TexAT) TPC in conjunction with the General Electronics for TPCs (GET) system. The benchmark case studied was that of 12 N β-decay to the first α-unbound state in 12 C, the Hoyle state. Here, half-life and branching ratio measurements are presented and are in good agreement with previous studies. The efficacy of using TPCs to study such a near-threshold state and disentangle the three-body dynamics of the decay products is demonstrated.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Investigation of the isoscalar monopole response in the proton-rich nucleus 14 O

Deuteron inelastic scattering on 14 O was measured in inverse kinematics using an active-target time projection chamber and a magnetic spectrograph. The experimental technique enabled precise measurements of deuteron recoiling particles in coincidence with beam-like fragments detected in the spectrograph focal plane. The double differential cross section was reconstructed for scattering angles of 3–6 degrees and excitation energies up to 26 MeV. The monopole strength distribution was obtained from the data using a multipole decomposition analysis. The results were compared to quasiparticle random-phase approximation (QRPA) and generator coordinate method (GCM) calculations. The QRPA calculation accurately describes experimental data in the energy range of 13 to 26 MeV. GCM calculations assuming a 12 C (g . s .) + p + p cluster configuration were used to determine the 0 + strength in 14 O below 13 MeV. The monopole transition strength of these cluster states provides a good description of the experimental distribution in the 9–11 MeV region, while the 0$^{+}_{2}$ state accounts for only a small fraction of the experimental strength around 6 MeV.

Active target↗

Model deformation system

The development of a system to measure model deflections encountered in the National Transonic Facility is discussed. The goal is to be able to measure peak deflections of up to 3 in. with accuracies to within 0.0025 in. over an area 1 m square as the model pitches through an included angle of 30 deg. Stereophotogrammetric techniques are being implemented, with the initial system being an extension of standard techniques. A second system, which will be all electronic, is under development. Both techniques require targets to be strategically placed on the model. Active targets are being developed for location in the model in order to maximize the signal-to-noise ratio and to approximate a point source. Image processing techniques and stereophotogrammetric data reduction programs are being implemented to perform the data reduction tasks.

Holmes, H. K.↗

Probe for selectively characterizing enzymes involved in xenobiotic metabolism and method of making and using the same

Activity-based probes that can be used to selectively identify and characterize enzymes that are involved in different phases of xenobiotic metabolism in a host and its microbiota population(s) are described. The activity-based probes described specifically label only their target active enzymes involved in xenobiotic metabolism and therefore provide a measurement of true protein functional activity rather than transcript or protein abundance. The activity-based probes also provide multimodal profiling of these active enzymes. Methods for preparing the activity based probes and exemplary methods for their use also are disclosed.

Wright, Aaron T.↗

Probe for selectively characterizing enzymes involved in xenobiotic metabolism and method of making and using the same

Activity-based probes that can be used to selectively identify and characterize enzymes that are involved in different phases of xenobiotic metabolism in a host and its microbiota population(s) are described. The activity-based probes described specifically label only their target active enzymes involved in xenobiotic metabolism and therefore provide a measurement of true protein functional activity rather than transcript or protein abundance. The activity-based probes also provide multimodal profiling of these active enzymes. Methods for preparing the activity based probes and exemplary methods for their use also are disclosed.

Wright, Aaron T.↗

Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy

Abstract Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic- co -glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([ 225 Ac]Ac 3+ ). Encapsulation of [ 225 Ac]Ac 3+ within PLGA nanoparticles (Z ave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [ 225 Ac]Ac 3+ . Chelation of [ 225 Ac]Ac 3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([ 225 Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [ 225 Ac]AcBLPhen significantly increased the delivery of [ 225 Ac]Ac 3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [ 225 Ac]Ac 3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles. Graphical Abstract

60 APPLIED LIFE SCIENCES↗

MSLICE Science Activity Planner for the Mars Science Laboratory Mission

MSLICE (Mars Science Laboratory InterfaCE) is the tool used by scientists and engineers on the Mars Science Laboratory rover mission to visualize the data returned by the rover and collaboratively plan its activities. It enables users to efficiently and effectively search all mission data to find applicable products (e.g., images, targets, activity plans, sequences, etc.), view and plan the traverse of the rover in HiRISE (High Resolution Imaging Science Experiment) images, visualize data acquired by the rover, and develop, model, and validate the activities the rover will perform. MSLICE enables users to securely contribute to the mission s activity planning process from their home institutions using off-the-shelf laptop computers. This software has made use of several plug-ins (software components) developed for previous missions [e.g., Mars Exploration Rover (MER), Phoenix Mars Lander (PHX)] and other technology tasks. It has a simple, intuitive, and powerful search capability. For any given mission, there is a huge amount of data and associated metadata that is generated. To help users sort through this information, MSLICE s search interface is provided in a similar fashion as major Internet search engines. With regard to the HiRISE visualization of the rover s traverse, this view is a map of the mission that allows scientists to easily gauge where the rover has been and where it is likely to go. The map also provides the ability to correct or adjust the known position of the rover through the overlaying of images acquired from the rover on top of the HiRISE image. A user can then correct the rover s position by collocating the visible features in the overlays with the same features in the underlying HiRISE image. MSLICE users can also rapidly search all mission data for images that contain a point specified by the user in another image or panoramic mosaic. MSLICE allows the creation of targets, which provides a way for scientists to collaboratively name features on the surface of Mars. These targets can also be used to convey instrument-pointing information to the activity plan. The software allows users to develop a plan of what they would like the rover to accomplish for a given time period. When developing the plan, the user can input constraints between activities or groups of activities. MSLICE will enforce said constraints and ensure that all mission flight rules are satisfied.

Powell, Mark W.↗

Multiplex knockout of trichome-regulating MYB duplicates in hybrid poplar using a single gRNA

As the focus for CRISPR/Cas-edited plants moves from proof-of-concept to real-world applications, precise gene manipulation will increasingly require concurrent multiplex editing for polygenic traits. A common approach for editing across multiple sites is to design one guide RNA (gRNA) per target; however, this complicates construct assembly and increases the possibility of off-target mutations. In this study, we utilized one gRNA to target MYB186, a known positive trichome regulator, as well as its paralogs MYB138 and MYB38 at a consensus site for mutagenesis in hybrid poplar (Populus tremula × P. alba INRA 717-1B4). Unexpected duplications of MYB186 and MYB138 resulted in eight alleles for the three targeted genes in the hybrid poplar. Deep sequencing and polymerase chain reaction analyses confirmed editing across all eight targets in nearly all of the resultant glabrous mutants, ranging from small indels to large genomic dropouts, with no off-target activity detected at four potential sites. This highlights the effectiveness of a single gRNA targeting conserved exonic regions for multiplex editing. Additionally, cuticular wax and whole-leaf analyses showed a complete absence of triterpenes in the trichomeless mutants, hinting at a previously undescribed role for the nonglandular trichomes of poplar.

59 BASIC BIOLOGICAL SCIENCES↗

Development of thermostable carbonic anhydrases using structure-guided recombination for use in CO2 removal systems on spacecraft

Carbon capture and storage has been a research area of great interest in recent years asa method for mitigation of CO2emissions, due to the effects of climate change. The development of technologies for the efficient capture of CO2are also of great interest for human spaceflight applications. One of the most promising technologies in this area is CO2 scrubbing using liquid amines, unfortunately, liquid amines with low heats of desorption tend to have slow CO2binding kinetics. One potential solution to this problem is to use the enzyme carbonic anhydrase (CA) to enhance the kinetics of CO2binding to liquid amines, allowing the overall process to be more energy efficient. Interest in using carbonic anhydrase as a biocatalyst has led to a number of efforts to improve the thermostability and solvent tolerance of several distinct carbonic anhydrase enzymes. In the work described here, we screened through a diverse set of natural carbonic anhydrases to identify candidates for protein engineering aimed at increased stability and activity in various liquid amines. We then used SCHEMA structure-guided recombination to develop a set of chimeric carbonic anhydrases with high thermostability and activity. These chimeras were used as the starting points for further protein engineering work targeting activity in liquid amine systems. Our ultimate goal is to test the engineered enzymes in a liquid amine system for cabin air revitalization on ISS or other spacecraft.

Life Support↗

Development of Thermostable Carbonic Anhydrases Using Structure-Guided Recombination for Use in CO2 Removal Systems on Spacecraft

Carbon capture and storage has been a research area of great interest in recent years as a method for mitigation of CO2 emissions, due to the effects of climate change. The development of technologies for the efficient capture of CO2 are also of great interest for human spaceflight applications. One of the most promising technologies in this area is CO2 scrubbing using liquid amines, unfortunately, liquid amines with low heats of desorption tend to have slow CO2 binding kinetics. One potential solution to this problem is to use the enzyme carbonic anhydrase (CA) to enhance the kinetics of CO2 binding to liquid amines, allowing the overall process to be more energy efficient. Interest in using carbonic anhydrase as a biocatalyst has led to a number of efforts to improve the thermostability and solvent tolerance of several distinct carbonic anhydrase enzymes. In the work described here, we screened through a diverse set of natural carbonic anhydrases to identify candidates for protein engineering aimed at increased stability and activity in various liquid amines. We then used SCHEMA structure-guided recombination to develop a set of chimeric carbonic anhydrases with high thermostability and activity. These chimeras were used as the starting points for further protein engineering work targeting activity in liquid amine systems. Our ultimate goal is to test the engineered enzymes in a liquid amine system for cabin air revitalization on ISS or other spacecraft.

Life Support, Carbon dioxide, Carbonic anhydrase, ↗

Evaluation of SR/ TEVA/ TRU triple stack for separation of activation products

A rapid method to separate Ta, Po, Au, Pt, and W from a sample containing mixed fission and activation products was developed using three commercially available extraction chromatography resins stacked in series. When the separation was tested using all the target activation products, even those with short half-lives were measurable. Finally, combining multiple extraction chromatography resin cartridges in tandem allows for multiple short-lived activation products to be separated from one sample addition without the complication of multiple steps.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Heterologous synthesis of the complex homometallic cores of nitrogenase P- and M-clusters in Escherichia coli

Nitrogenase is an active target of heterologous expression because of its importance for areas related to agronomy, energy, and environment. One major hurdle for expressing an active Mo-nitrogenase in Escherichia coli is to generate the complex metalloclusters (P- and M-clusters) within this enzyme, which involves some highly unique bioinorganic chemistry/metalloenzyme biochemistry that is not generally dealt with in the heterologous expression of proteins via synthetic biology; in particular, the heterologous synthesis of the homometallic P-cluster ([Fe 8 S 7 ]) and M-cluster core (or L-cluster; [Fe 8 S 9 C]) on their respective protein scaffolds, which represents two crucial checkpoints along the biosynthetic pathway of a complete nitrogenase, has yet to be demonstrated by biochemical and spectroscopic analyses of purified metalloproteins. Here, we report the heterologous formation of a P-cluster-containing NifDK protein upon coexpression of Azotobacter vinelandii nifD, nifK, nifH, nifM, and nifZ genes, and that of an L-cluster-containing NifB protein upon coexpression of Methanosarcina acetivorans nifB, nifS, and nifU genes alongside the A. vinelandii fdxN gene, in E. coli. Our metal content, activity, EPR, and XAS/EXAFS data provide conclusive evidence for the successful synthesis of P- and L-clusters in a nondiazotrophic host, thereby highlighting the effectiveness of our metallocentric, divide-and-conquer approach that individually tackles the key events of nitrogenase biosynthesis prior to piecing them together into a complete pathway for the heterologous expression of nitrogenase. As such, this work paves the way for the transgenic expression of an active nitrogenase while providing an effective tool for further tackling the biosynthetic mechanism of this important metalloenzyme.

59 BASIC BIOLOGICAL SCIENCES↗

Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding

Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC binding affinity, retain FXa-enzymatic activity and reduce the DOAC-associated bleeding by restoring hemostasis in mice treated with apixaban. Importantly, the FXaDOACs reversal agents we designed, unlike andexanet alfa, do not inhibit TFPI, and consequently, may have a safer thrombogenic profile.

59 BASIC BIOLOGICAL SCIENCES↗

International Education Opportunities during the IHY: Bridging the Geographic, Cultural and Linguistic Divide between Participating IHY Nations

Currently there are over 70 U.N. Member States participating in the International Heliophysical Year (IHY 2007- 8), and most of these nations do not use English as their primary language. The IHY contains four main program elements: Science, Observatory Development, Outreach, and History. For these elements to be successful, each requires successful communication within and adaptation for the individual member states. The IHY Outreach program contains many educational activities targeting a wide range of languages and contexts. The other three program elements, however, offer a means to extend the impact of the educational programs and reinforce educational activities. IHY's scientific activities involve partnerships with institutions and observatories, many of which have outreach activities in their local communities. Scientists and participation programs from around the world have begun translating materials into their local languages and adapting educational tools for use in their communities. IHY's Observatory Development program, which began deploying instrumentation worldwide in 2004, encourages a strong educational component to each new observatory site as a means of ensuring long-lasting viability of the research program. The history program gathers important information and educates the public about the development of space science. This presentation will discuss efforts occurring within the IHY program that support cross-cultural communication and education and present opportunities to reach new audiences.

Thompson, B.J.↗

Dispatching Grid-Forming Inverters in Grid-Connected and Islanded Mode

This paper explores the dispatchability of grid-forming (GFM) inverters in grid-connected and islanded mode. GFM inverters usually use droop control to automatically share power with other GFM sources (inverters and synchronous generators) and follow the change in the load demand; however, they can be dispatched like their grid-following (GFL) counterparts to output the target active and reactive power. This will help grid operators better manage their inverter-based resources (IBRs) to improve operation efficiency and reliability; therefore, this paper proposes an innovative concept of dispatching GFM sources (inverters and synchronous generators) to output the target power in both grid-connected and islanded mode by adjusting their droop intercepts. The fundamental principle is that the GFM inverter's active and reactive power is dictated by its frequency and voltage, and thus dispatching the active and reactve power of a GFM inverter can be achieved through dispatching its frequency and voltage. Moreover, the concept distinguishes the dispatch rules for grid-connected and islanded mode. Finally, the concept is validated with an example microgrid system with two GFM inverters, one diesel generator, one GFL inverter, and the load in both grid-connected and islanded mode. This pioneering work results in practical guidance for the development of energy management systems for future electric grids with GFM and GFL inverters.

dispatching↗

Discovery and Development of a Small-Molecule Inhibitor Targeting the GAS41 YEATS Domain in Nonsmall Cell Lung Cancer

Abstract GAS41 is frequently overexpressed in Non-Small Cell Lung Cancer (NSCLC). GAS41 contains a YEATS domain, which recognizes acetylated lysine residues on histones to recruit protein complexes and facilitate transcription. Suppression of GAS41 in NSCLC models inhibits cellular proliferation and markedly reduces tumor growth in mouse xenografts, justifying the development of small-molecule inhibitors. We have employed structure-based design and medicinal chemistry optimization to discover DLG-41, a submicromolar inhibitor binding to the GAS41 YEATS domain. DLG-41 potently disrupts the association of GAS41 YEATS with chromatin in mammalian cells and inhibits the proliferation of NSCLC cell lines with submicromolar potency without significantly affecting normal lung fibroblasts. DLG-41 induces more effective growth inhibition in A549 versus GAS41-knockout cells, demonstrating on-target activity. DLG-41 treatment upregulates the CDKN1A gene and downregulates pathways associated with lung cancer cell identity, tumor migration, and invasion. DLG-41 is a promising chemical probe for targeting GAS41 protein in NSCLC models and has potential for future development.

Listunov, Dymytrii [University of Michigan , , , ,↗

Dispatching Grid-Forming Inverters in Grid-Connected and Islanded Mode: Preprint

This paper explores the dispatch-ability of grid-forming (GFM) inverters in grid-connected and islanded mode. Grid-forming (GFM) inverters usually use droop control to automatically share power with other GFM sources (inverters and synchronous generator (SG)) and follow the change of the load demand. However, they can be dispatched like their grid-following (GFL) counterparts to output the target active and reactive power. This will help the grid operator better manage their inverter-based resources (IBRs) for improved operation efficiency and reliability. Therefore, this paper proposes an innovative concept of dispatching GFM sources (inverters and SG) to output the target power for both grid-connected and islanded mode by adjusting their droop intercepts. The fundamental principle of doing so is that the GFM inverter's active and reactive power is dictated by its frequency and voltage, thus, dispatching active and reactve power of a GFM inverter can be achieved through dispatching its frequency and voltage. Moreover, the concept distinguishes the dispatch rules for grid-connected and islanded mode. Finally, the concept is validated with an example microgrid system with two GFM inverters, one diesel generator, one grid-following inverter and loads in both grid-connected and islanded mode. This pioneering work results in a practical guidance for power system energy management system (EMS) development to control a future grid with GFM and GFL inverters.

droop control↗