Search NASA⌕ Search

SEARCH · Search NASA

Results for “CARTs”

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 19 records

Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)

Safe and effective DNA delivery systems are required to enable or enhance clinical strategies and research involving gene therapy and DNA vaccinations. To address this delivery problem, a series of charge-altering releasable transporters (CARTs) with varied lipid content were prepared and evaluated for plasmid DNA (pDNA) delivery into cultured cells. These lipid-modified CART co-oligomers were synthesized in only two steps via sequential organocatalytic ring-opening polymerization of lipid-containing cyclic carbonate monomers and morpholinone monomers. Lipid variations of the CARTs substantially impacted the delivery efficiency of pDNA, with oleyl- and linoleyl-based CARTs showing enhanced performance relative to the commercial transfection agent Lipofectamine 2000 (L2000). The best-performing oleyl CART was carried forward to study stable luciferase transfection with a Sleeping Beauty (SB) transposon system. The oleyl CART outperformed the L2000 positive control with respect to stable transfection efficiency. CART-pDNA complexes represent a new DNA delivery system for research and clinical applications.

59 BASIC BIOLOGICAL SCIENCES↗

CART peptide activates the Nrf2/HO-1 antioxidant pathway and protects hippocampal neurons in a rat model of Alzheimer's disease

Highlights: • CART peptide reduced the accumulation of Aβ in the hippocampus of AD rats. • CART peptide improved the cognitive function of AD rats. • CART peptide attenuated the oxidative stress damage in the hippocampus of AD rats. • CART activated the Nrf2/HO-1 pathway to exert antioxidation. • CART inhibit the apoptosis of hippocampal neurons. The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ{sub 1-42} (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0.02μg/hemisphere) into rat hippocampus was administered for five consecutive days before Aβ{sub 1-42} treatment. We found that Aβ{sub 1-42} microinjection led to reduction of endogenous CART level in rat hippocampus. CART pretreatment improved the spatial memory and locomotor ability of AD rats. CART peptide decreased the Aβ{sub 1-42} and Aβ production-associated enzyme BACE1 levels. Moreover, CART peptide attenuated the oxidative stress damage with a concrete manifestation of increased MDA as well as decreased T-SOD, GSH and ATP levels in the hippocampus of Aβ{sub 1-42}-treated rat, which may be causatively implicated the activating of Nrf2/HO-1 signaling pathway. Furthermore, CART peptide attenuated neuronal apoptosis with decreased Bax, caspase-9 and caspase-3 levels and increased Bcl-2 level in rat hippocampus. Our results therefore indicate that CART peptide could serve as an antioxidant in early therapy for AD.

60 APPLIED LIFE SCIENCES↗

New developments of the CARTE thermochemical code: A two-phase equation of state for nanocarbons

We developed a new equation of state (EOS) for nanocarbons in the thermodynamic range of high explosives detonation products (up to 50 GPa and 4000 K). This EOS was fitted to an extensive database of thermodynamic properties computed by molecular dynamics simulations of nanodiamonds and nano-onions with the LCBOPII potential. We reproduced the detonation properties of a variety of high explosives with the CARTE thermochemical code, including carbon-poor and carbon-rich explosives, with excellent accuracy.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

FY16 Safeguards Technology Cart-Portable Mass Spectrometer Project Final Report

The Oak Ridge National Laboratory project for the Next Generation Safeguards Initiative Safeguards Technology Development Subprogram has been involved in the development of a cart portable mass spectrometer based on a Thermo ITQ ion trap mass spectrometer (referred to simply as the ITQ) for the field analysis of 235U/238U ratios in UF6. A recent discovery of the project was that combining CO2 with UF6 and introducing the mixture to the mass spectrometer (MS) appeared to increase the ionization efficiency and, thus, reduce the amount of UF6 needed for an analysis while also reducing the corrosive effects of the sample. However, initial experimentation indicated that mixing parameters should be closely controlled to ensure reproducible results. To this end, a sample manifold (SM) that would ensure the precise mixing of UF6 and CO2 was designed and constructed. A number of experiments were outlined and conducted to determine optimum MS and SM conditions which would provide the most stable isotope ratio analysis. The principal objective of the project was to provide a retrofit ITQ mass spectrometer operating with a SM capable of achieving a variation in precision of less than 1% over 1 hour of sampling. This goal was achieved by project end with a variation in precision of 0.5 to 0.8% over 1 hour of sampling.

47 OTHER INSTRUMENTATION↗

Residual Dose Rates Analyses from Vent Lines Shield Block on the Target Cart at Spallation Neutron Source

The target carriage supports the mercury target vessel in the Spallation Neutron Source (SNS) in a cantilevered fashion and supplies the liquid mercury flowing to and from the target vessel. The target carriage is designed to move the target vessel into its target monolith position to receive the proton beam and then remove it horizontally back into an adjacent service cell, where the target vessel can be exchanged about 2-3 times per calendar year. At the time of the performed studies, the SNS mercury target can accept a proton beam at 1 GeV energy and 1.4 MW power; however, it will be upgraded to receive 1.3 GeV energy at 2 MW by the end of 2024 year [1]. The cart is practically a shield block on wheels to minimize fluxes and dose rates in the service cell downstream of the carriage. There are vent lines located inside a passage on top of the target carriage, and they are covered by a stepping-up steel shield block (vent lines shield block). Vent lines are permanently attached to the shield block. New vent lines with a different design are going to be installed. These lines are shielded by the new steel block to which the vent lines are attached. The estimate of the residual dose rates from the block after it is extracted from the target carriage is performed to estimate the radiation fields and to decide on the type of storage container to be used.

Popova, Irina I↗

“Beam à la carte”: Laser heater shaping for attosecond pulses in a multiplexed x-ray free-electron laser

Electron beam shaping allows the control of the temporal properties of x-ray free-electron laser pulses from femtosecond to attosecond timescales. Here, we demonstrate the use of a laser heater to shape electron bunches and enable the generation of attosecond x-ray pulses. We demonstrate that this method can be applied in a selective way, shaping a targeted subset of bunches while leaving the remaining bunches unchanged. This experiment enables the delivery of shaped x-ray pulses to multiple undulator beamlines, with pulse properties tailored to specialized scientific applications.

43 PARTICLE ACCELERATORS↗

Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals

Significance Protein expression using mRNA has the potential to transform many areas of life science research and affect the prevention, detection, and treatment of disease. However, realizing this potential requires the development of readily accessible, efficacious, and safe delivery systems that can functionally deliver mRNA to cells in culture and in vivo. A class of materials developed for mRNA delivery is described that operates through an unprecedented self-immolation mechanism. These materials are accessed in two steps through an organocatalytic oligomerization. They noncovalently complex, protect, deliver, and release mRNA with >99% transfection efficiency in cultured cells and with robust protein expression in mice using multiple routes of administration. This mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.

59 BASIC BIOLOGICAL SCIENCES↗

High Insulating Vacuum Pump Cart Analysis

To maintain superconductive and cryogenic temperature, it is necessary to utilize high vacuum to eliminate convective heat transfer. To reach the desirable pressure of 10^-6 Torr at a reasonable time, the vacuum pumps and vessel geometry are evaluated for compatibility. Based on the analysis, a list of dry scroll pumps and turbomolecular pumps are recommended.

Chicas, Kelly [Illinois U., Urbana]↗

Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters

We report a strategy for generating a combinatorial library of oligonucleotide transporters with varied lipid domains and their use in the efficient transfection of lymphocytes with mRNA in vitro and in vivo. This library is based on amphiphilic charge-altering releasable transporters (CARTs) that contain a lipophilic block functionalized with various side-chain lipids and a polycationic α-amino ester mRNA-binding block that undergoes rearrangement to neutral small molecules, resulting in mRNA release. We show that certain binary mixtures of these lipid-varied CARTs provide up to a ninefold enhancement in mRNA translation in lymphocytes in vitro relative to either a single-lipid CART component alone or the commercial reagent Lipofectamine 2000, corresponding to a striking increase in percent transfection from 9–12% to 80%. Informed by the results with binary mixtures, we further show that CARTs consisting of optimized ratios of the two lead lipids incorporated into a single hybrid-lipid transporter molecule maintain the same delivery efficacy as the noncovalent mixture of two CARTs. The lead lipid CART mixtures and hybrid-lipid CARTs show enhanced lymphocyte transfection in primary T cells and in vivo in mice. This combinatorial approach for rapidly screening mRNA delivery vectors has provided lipid-varied CART mixtures and hybrid-lipid CARTs that exhibit significant improvement in mRNA delivery to lymphocytes, a finding of potentially broad value in research and clinical applications.

59 BASIC BIOLOGICAL SCIENCES↗

Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy

Treating macaques with an anti-α4β7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4β7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4β7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4β7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4β7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed—some animals exhibited large fluctuations in viral load after cART cessation—the model suggests that anti-α4β7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.

60 APPLIED LIFE SCIENCES↗

A Synchronized Sensor Array for Remote Monitoring of Avian and Bat Interactions with Offshore Renewable Energy Facilities

Wind energy production in the U.S. is projected to increase to 35% of our nation’s energy by 2050. This substantial increase in the U.S. is only a portion of the global wind industry growth, as many countries strive to reduce greenhouse gas emissions. A major environmental concern and potential market barrier for expansion of wind energy is bird and bat mortality from impacts with turbine blades, towers, and nacelles. Carcass surveys are the standard protocol for quantifying mortality at onshore sites. This method is imperfect, however, due to survey frequency at remote sites, removal of carcasses by scavengers between surveys, searcher efficiency, and other biases as well as delays of days to weeks or more in obtaining information on collision events. Furthermore, carcass surveys are not feasible at offshore wind energy sites. Near-real-time detection and quantification of interaction rates is possible at both onshore and offshore wind facilities using an onboard, integrated sensor package with data transmitted to central processing centers. We developed and experimentally tested an array of sensors that continuously monitors for interactions (including impacts) of birds and bats with wind turbines. The synchronized array includes three sensor nodes: (1) vibration (accelerometers and contact microphones), (2) optical (visual and infrared spectrum cameras), and (3) bioacoustics (acoustic and ultrasonic microphones). Accelerometers and contact acoustic microphones are placed at the root of each blade to detect impact vibrations and sound waves propagating through the structure. On-board data processing algorithms using wavelet analysis detect impact signals exceeding background vibration. Stereo-visual and infrared cameras were placed on the nacelle to allow target tracking, distance, and size calculations. On-board image processing and target detection algorithms identify moving targets within the camera field of view. Bioacoustic recorders monitor vocalizations and echolocations to aid in identifying organisms involved in interactions. Data from all sensors are temporarily stored in ring (i.e., circular) buffers with a duration varying by sensor type. Detection of target presence or impact by any of the sensors can trigger the archiving of data from all buffers for transmission to a central data processing center for evaluation and post-processing. This mitigates the risk of “data mortgages” posed by continual recording and minimizes personnel time required to manually review event data. We first conducted individual component tests at laboratories and field sites in Corvallis and Newport, Oregon, and Seattle and Sequim, Washington. We conducted additional component tests on research wind turbines at the North American Wind Research and Training Center, Mesalands Community College (MCC; General Electric 1.5 MW turbine), New Mexico, and the National Wind Technology Center, National Renewable Energy Laboratory (NREL; Controls Advanced Research Turbines 3 [CART 3] 600 kW Westinghouse turbine), Colorado. We conducted fully integrated system tests at NREL in October 2014 and April 2015. We used only research wind turbines so that we could conduct controlled, experimentally generated impacts using empty and water-filled tennis balls shot from a compressed air cannon on the ground. The approx. 57-140 g tennis balls (depending on water content) were at the upper mass range for bats, but lower mass range for marine birds. Therefore, the ability to detect collisions of most seabirds is likely greater than our experiments demonstrate, but possibly lower for some bats depending on the background signal of a given turbine. Vibration data demonstrated that background signals of operating turbines varied markedly among the CART 3 under normal operation (greatest), GE (moderate), and CART 3 during idle rotation (generator not engaged; least). In total, we measured 63 experimental blade impacts on the two research turbines. Impaction detection was dependent on background signals, position of impact on the blade (a tip strike resulted in the strongest impact signal), and impact kinetics (velocity of ball and whether the ball struck the surface of the blade or the leading edge of the blade struck the ball). Overall detection percentage ranged from 100% for the “quietest” conditions (CART 3 idle rotation), down to 35% for the noisiest (CART 3 normal operation). Impact signals were detected from sensors on more than one blade (i.e., blades other than the blade struck) 50% - 75% of the time. Stereo imaging provided valuable metrics, but increased data processing and equipment cost. Given the cost of cameras with sufficient resolution for target identification, we suggest mounting cameras directly on the blades to continuously view the entire rotor swept area with the fewest number of cameras. Bioacoustic microphones provide taxonomic identification, as well as information on ambient noise levels. They also assist in identifying environmental conditions such as hail storms, high winds, thunder, lightning, etc., that may contribute to a collision or a false positive detection. We demonstrated a proof of concept for an integrated sensor array to detect and identify bird and bat collisions with wind turbines. The next phase of research and development for this system will miniaturize and integrate sensors from all three nodes into a single wireless package that can be attached directly to the blade. This next generation system would use all “smart” sensors capable of onboard data processing to drastically reduce data streams and processing time on a central computer. A provisional patent for the blade mounted system was submitted by Oregon State University and recorded by the U.S. Patent and Trademark Office (application no. 62313028). Eventually, technology and industry advances will allow this low cost monitoring system to be designed into materials during manufacturing so that all turbines could be monitored with either a subset or full suite of sensors. As standard equipment on all commercial turbines, the sensor suite would allow the industry to effectively monitor whether individual turbines were causing mortalities or not and under what circumstances. It would also provide real-time evaluation of mechanical and structural integrity of a turbine via vibration, image, and acoustic data streams, thereby permitting modifications in operation to limit environmental or mechanical damage.

17 WIND ENERGY↗

Structural and pharmacological evaluation of a novel non-nucleoside reverse transcriptase inhibitor as a promising long acting nanoformulation for treating HIV

Combination antiretroviral therapy (cART) has been proven effective in inhibiting human immunodeficiency virus type 1 (HIV-1) infection and has significantly improved the health outcomes in acquired immune deficiency syndrome (AIDS) patients. The therapeutic benefits of cART have been challenged because of the toxicity and emergence of drug-resistant HIV-1 strains along with lifelong patient compliance resulting in non-adherence. These issues also hinder the clinical benefits of non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are one of the vital components of cART for the treatment of HIV-1 infection. In this work, using a computational and structural based drug design approach, we have discovered an effective HIV -1 NNRTI, compound I (Cmpd I) that is very potent in biochemical assays and which targets key residues in the allosteric binding pocket of wild-type (WT)-RT as revealed by structural studies. Furthermore, Cmpd I exhibited very potent antiviral activity in HIV-1 infected T cells, lacked cytotoxicity (therapeutic index >100,000), and no significant off-target effects were noted in pharmacological assays. To address the issue of non-adherence, we developed a long-acting nanoformulation of Cmpd I (Cmpd I-NP) using poly (lactide-coglycolide) (PLGA) particles. The pharmacokinetic studies of free and nanoformulated Cmpd I were carried out in BALB/c mice. Intraperitoneal administration of Cmpd I and Cmpd I-NP in BALB/c mice revealed prolonged serum residence time of 48 h and 30 days, respectively. The observed serum concentrations of Cmpd I in both cases were sufficient to provide >97% inhibition in HIV-1 infected T-cells. The significant antiviral activity along with favorable pharmacological and pharmacokinetic profile of Cmpd I, provide compelling and critical support for its further development as an anti-HIV therapeutic agent.

60 APPLIED LIFE SCIENCES↗

Approximate Mixed-Integer Programming Solution with Machine Learning Technique and Linear Programming Relaxation

Security constrained unit commitment (SCUC) is solved in the day-ahead electricity market to determine electricity generation schedule for the following date. The associated mixed integer programming (MIP) problem is known computationally hard. Heuristics like rounding can be computationally efficient for solving large MIP problems however often produces lower quality solutions due to discrepancy between MIP solution and linear programming relaxation (LPR) solution, i.e., variables taking different discrete values between MIP and LPR solutions. In this work, we applied the machine learning-based algorithms—Classification and Regression Tree (CART) model and random forest (RF) model—to obtain an LPR-based approximation that close to an MIP solution without actually solving the MIP problem. By computing feature importance derived from the CART and RF models, we assessed the link between coefficients in the MIP model, the LPR solution, and the optimal solution of the MIP problem. We applied the CART and RF approaches to solve SCUC problems using day-ahead energy market cases from Midcontinent Independent System Operator. The results show that our method is computationally efficient and could achieve an approximation sufficiently close to the SCUC solution with <0.15% error and ~78% reduction in the discrepancies between LPR and MIP solutions.

Lin, Xinming↗

Atmospheric Line of Site Experiment (ALOSE) Final Campaign Summary

The Atmospheric Line of Site Experiment (ALOSE) was a project to produce best-estimate atmospheric state measurements at the: 1. DOE Atmospheric Radiation Measurement (ARM) Clouds and Radiation Test-bed (CART) site located in Lamont, Oklahoma (11–14 December 2012) 2. Poker Flat Alaska Research Range (PFRR) located in Poker Flat, Alaska (19–26 February 2013) 3. DOE ARM CART site located in Lamont, Oklahoma (24–28 April 2013) 4. DOE ARM CART site located in Lamont, Oklahoma (9–15 July 2013) 5. DOE ARM Tropical Western Pacific (TWP) site located in Darwin, Australia (27 September–3 October 2013).

54 ENVIRONMENTAL SCIENCES↗