Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “activity generation”

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 847 records · Page 47

Investigation into Reductive Separation of Tc-99 from Low Activity Waste Off-Gas Condensate by Zero Valent Iron Materials - 20311

This study is investigating the potential for reductive separation of technetium-99 (Tc) from off-gas condensate generated from vitrification of legacy tank waste at the Hanford Tank Waste Treatment and Immobilization Plant. Management of Tc is a high-priority activity for the U.S. Department of Energy (DOE) Office of Environmental Management (EM) complex, which must be addressed based on knowledge gaps and technology development needs outlined in the DOE-EM Technetium Management Program Plan [1]. Technetium is one of the main risk drivers in the permanent disposal of low activity waste (LAW) by vitrification at the Hanford Site due to its high volatility and only fractional incorporation into borosilicate glass. Volatilized Tc will be captured by an off-gas treatment system, and the current plan is to continuously recycle generated condensate back to the LAW glass melter feed. Off-gas recycling is effective at increasing Tc loading in the LAW glass, but it also disproportionately increases concentrations of sulfate, halides, and other volatile compounds impeding overall LAW processing leading to significantly greater waste glass volume requirements. Removal of Tc from secondary liquid waste offers an alternative disposal route to continuous off-gas recycling which may result in significant reduction of the volumes of LAW waste glass and substantial cost savings. The objective of this research funded by the DOE-EM Minority Serving Institutions Partnership Program (MSIPP) is to determine the suitability of zero valent iron (ZVI) as a separation technology to remove Tc from the off-gas condensate stream to minimize its recycle. While ZVI has been proposed for various remediation applications with Tc, it has not been studied for its suitability for removing Tc from the LAW off-gas condensate. The goal is to identify the optimal conditions for which Tc{sup (VII)} will be reduced to Tc{sup (IV)} species and incorporated into an iron matrix. This paper presents a programmatic overview of our evaluation of commercial ZVI materials for their efficiency towards Tc{sup (VII)} reductive removal from simplified off-gas simulant solutions under aerobic conditions. Tc concentrations in solutions were monitored for up to 30 days to determine efficiency and kinetics of reductive removal of Tc. The best performing candidate materials were selected for further experiments evaluating the effects of (1) variable ionic strength, (2) the presence of chromium and corrosive anions, and (3) ZVI aging on Tc{sup (VII)} reductive removal in batch experiments. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Emerging Soluble Organic Redox Materials for Next-Generation Grid Energy-Storage Applications

Soluble organic redox molecules have emerged as promising candidate active materials for multiple energy storage systems due to their structural versatility, fast redox process, high capacity storage, sustainability, and environmental friendliness. This review examines recent progress in developing such materials in green and sustainable batteries for grid applications and points out directions for future research.

Zhan, Xiaowen↗

Machine-learned interatomic potentials by active learning: amorphous and liquid hafnium dioxide

We propose an active learning scheme for automatically sampling a minimum number of uncorrelated configurations for fitting the Gaussian Approximation Potential (GAP). Our active learning scheme consists of an unsupervised machine learning (ML) scheme coupled with a Bayesian optimization technique that evaluates the GAP model. We apply this scheme to a Hafnium dioxide (HfO 2 ) dataset generated from a "melt-quench" ab initio molecular dynamics (AIMD) protocol. Our results show that the active learning scheme, with no prior knowledge of the dataset, is able to extract a configuration that reaches the required energy fit tolerance. Further, molecular dynamics (MD) simulations performed using this active learned GAP model on 6144 atom systems of amorphous and liquid state elucidate the structural properties of HfO 2 with near ab initio precision and quench rates (i.e., 1.0 K/ps) not accessible via AIMD. The melt and amorphous X-ray structural factors generated from our simulation are in good agreement with experiment. In addition, the calculated diffusion constants are in good agreement with previous ab initio studies.

36 MATERIALS SCIENCE↗

Multilayered regulation by RNA thermometers enables precise control of Cas9 expression in E. coli

Cas9-based genome editing technologies can rapidly generate mutations to probe a diverse array of mutant genotypes. However, aberrant Cas9 nuclease translation and activity can occur despite the use of inducible promoters to control expression, leading to extensive cell death. This background killing caused by promoter leakiness severely limits the application of Cas9 for generating mutant libraries because of the potential for population skew. We demonstrate the utility of temperature sensitive RNA elements as a layer of post-transcriptional regulation to reduce the impact of promoter leak. We observe significant temperature-dependent increases in cell survival when certain RNA thermometers (RNATs) are placed upstream of the cas9 coding sequence. We also show that the most highly repressing RNAT, hsp17rep, significantly reduces population skew with a library of characterized guide RNAs in Escherichia coli. This strategy should be applicable to all bacterial Cas9-based methods and technologies.

Kammerdiener, Elise K. [Oak Ridge National Laborat↗

A 150-kW 99% Efficient All-Silicon-Carbide Triple-Active-Bridge Converter for Solar-Plus-Storage Systems

Solar-plus-storage systems could effectively mitigate the uncertainties of the photovoltaic (PV) generation and improve system reliability by adding an integrated battery energy storage system. As a three-port bidirectional isolated dc–dc converter with soft-switching capability, the triple-active-bridge (TAB) converter inherently matches the requirements of the solar-plus-storage system. However, challenges still remain in the TAB converter design to further improve system efficiency. In this article, the detailed design, implementation, and demonstration for a silicon carbide (SiC) 150-kW TAB converter are presented. Starting from a brief review of the TAB converter, the modulation scheme, power characteristics, and soft-switching region are analyzed. Then, the detailed design of the H-bridge converter building block is given. Here, to improve the system efficiency, a comprehensive characterization of the SiC gate driver with various external gate resistances is performed to address tradeoffs between switching loss and voltage overshoot during transients, as well as the thermal performance of the H-bridge building block. In addition, the design and characterization of the 20-kHz three-port transformer are also given. Comprehensive experimental studies are conducted on a full-power prototype to verify the proposed design. With a measured 99.1% peak efficiency, the proposed TAB converter can fulfill the requirements for solar-plus-storage applications.

14 SOLAR ENERGY↗

Insights into activators on biomass-derived carbon-based composites for electrochemical energy storage

Biomass-derived carbon materials are now an essential source of carbon electrodes for high-performance supercapacitors due to their cost-effectiveness and abundant heteroatom self-doping properties. When preparing porous carbon materials from biomass for supercapacitor use, the use of activators can significantly increase the specific surface area of carbon materials, enhance pore structures, introduce more heteroatoms, promote the generation of various functional groups, and play a crucial role in the capacitance performance of biomass-derived carbon materials. However, the role of activators during the activation process has been overlooked in previous work focused on improving supercapacitor capacitance performance. In addition, there is a lack of comprehensive reviews summarizing the role of activators. Therefore, this work classifies the types of activators, discusses their activation mechanisms, operability, economy, and environmental friendliness, and proposes future development directions for activators. The main mixing methods of activators and carbon materials are also demonstrated, highlighting the advantages and disadvantages of each method. In conclusion, this work could provide valuable insights for the development of activators for high-performance supercapacitors.

25 ENERGY STORAGE↗

Modernizing the Nuclear Industry and New Ways of Working

Nuclear energy is recognized as the most feasible energy source towards achieving nation-wide net-zero goals (COP 208, MIT). Additionally, the demand for reliable, consistent energy supply is soaring with the construction of energy hungry data centers and AI tools. This means the construction of new nuclear and the continuation of current nuclear are a high national priority. However, this leaves the nuclear industry with a workforce challenge. The rising demand for nuclear power is threatened by an underpopulated workforce. There exist a few contributors to the decreased workforce such as skewed workforce demographics resulting in large-scale workforce retirement. Also, some plants have observed difficulty hiring and retaining skill sets that typically comprise the nuclear power workforce – specifically skilled craftsman. Those who are graduating with desirable skills are seeking employment in sectors that are more modern and culturally more aligned with younger generational values. Lastly, within the nuclear sector, skilled employees will be a competitive commodity as advanced plants come online offering work environments that incorporate modern technologies, skill sets, and opportunities for career advancement. These factors emphasize the need for legacy plants to modernize with a focus on the workplace environment and culture that meets younger generations’ skills, cultural expectations, and desire for advancement opportunities. Nuclear plants are actively engaged in deploying advancements that improve the management of systems, structures, and components as well as process improvements and technologies that can reduce the costs of operation and maintenance. However, the advancements must also be analyzed, reviewed and deployed in a manner that considers the impact on how people within the organization collaborate, communicate, make decisions, and solve problems. Neglecting to consider the cultural impact of modernization risks poor adoption, unrealized opportunities, or insignificant change toward helping attract new employees. The traditional way of working is not necessarily the way new generations want to engage with their employer. For instance, in a survey performed by North American Young Generation in Nuclear the top three reasons for younger nuclear employees to seek other job opportunities was seeking better work-life balance, a lack of advancement opportunities, and work culture and leadership style differences (Smyth et al. 2022). Integrated Operations for Nuclear (ION) is an approach for the nuclear industry to create long-term strategic modernization plans and analyze each advancement for the impact on people and processes and measure how those impacts flow up to support high-level, long-term plant goals and requirements. One principle of ION is to replace the current labor-centric operation style in legacy nuclear plants with data-centric collaborative operation styles. This paper will explain how transitioning operations to leverage centralized skills and responsibility, multi-skilled teams, and collaborative decision making can flatten the hierarchical structure in plants, enable greater individual efficacy while also offering more experiences and advancement opportunities to staff. Adopting the ION way of working shifts the industry mind-set towards more networked, collaborative, and modern way of working that will attract skilled, next-generation workers to operate the legacy nuclear fleet.

99 - GENERAL AND MISCELLANEOUS↗

Amphiphilic Baskets for Supramolecular Nanoarchitectures at Interfaces: Inverted Monolayer Formation on Water

Interfacial chemistry of molecular baskets remains poorly understood despite their promise for supramolecular applications of detection and sequestration of toxic molecules including those of illicit drugs, organophosphorus compounds, and anticancer agents. We present a fundamental investigation of the interfacial behavior of three amphiphilic supramolecular baskets (ASB 4, 8, and 12), having increasingly longer yet linear alkyl chains at the top of their bowl-shaped cavity. The studies were completed at the air−water interface to elucidate surface activity, interfacial stability, self-assembly, and monolayer organization that drive inverted monolayer formation, in which the molecular arms orient toward the aqueous phase in a configuration opposite to that typically observed for lipids. Herein, surface pressure−area isotherms of ASB 4, 8, 12, deposited on a water surface, were performed in tandem with nonequilibrium relaxation experiments to quantify surface activity, thermodynamic stability, and monolayer compressibility of the baskets’ monolayer assembly. Brewster angle microscopy enabled direct visualization of morphological evolution, aggregation, and packing at the interface. We show that systematic extension of the hydrocarbon arms, from four to 12 methylene groups, progressively modifies intermolecular packing, drives distinct two-dimensional aggregation pathways, and increases number densities at the air−water interface. Atomistic molecular dynamics simulations corroborate many of these experimentally observed trends and provide mechanistic detail on the cooperative roles of basket topology and interfacial concentration in regulating the hydration structure and dynamics within the cavities generated by surface-adsorbing baskets, consistent with observed variations in surface activity and packing. Our results establish how the topology of these unique supramolecules and their concentration govern interfacial organization and offer a rational framework for designing amphiphiles with predictable behavior at soft interfaces.

Hydrocarbons↗

Generation of Tin-Vacancy Centers in Diamond via Shallow Ion Implantation and Subsequent Diamond Overgrowth

Group IV color centers in diamond have garnered great interest for their potential as optically active solid-state spin qubits. The future utilization of such emitters requires the development of precise site-controlled emitter generation techniques that are compatible with high-quality nanophotonic devices. This task is more challenging for color centers with large group IV impurity atoms, which are otherwise promising because of their predicted long spin coherence times without a dilution refrigerator. For example, when applied to the negatively charged tin-vacancy (SnV – ) center, conventional site-controlled color center generation methods either damage the diamond surface or yield bulk spectra with unexplained features. Here we demonstrate a novel method to generate site-controlled SnV – centers with clean bulk spectra. We shallowly implant Sn ions through a thin implantation mask and subsequently grow a layer of diamond via chemical vapor deposition. This method can be extended to other color centers and integrated with quantum nanophotonic device fabrication.

36 MATERIALS SCIENCE↗

Silicon-On-Sapphire Metasurfaces Generate Arrays of Dark and Bright Traps for Neutral Atoms

We demonstrated crystalline silicon-on-sapphire (c-SOS) metasurfaces that convert a Gaussian beam into arrays of complex optical traps, including arrays of optical bottle beams that trap atoms in dark regions interleaved with bright tweezer arrays. The high refractive index and indirect band gap of crystalline silicon make it possible to design high-resolution near-infrared (λ > 700 nm) metasurfaces that can be manufactured at scale using CMOS-compatible processes. Compared with active components like spatial light modulators (SLMs) that have become widely used to generate trap arrays, metasurfaces provide an indefinitely scalable number of pixels, enabling large arrays of complex traps in a very small form factor, as well as reduced dynamic noise. To design metasurfaces that can generate three-dimensional bottle beams to serve as dark traps, we modified the Gerchberg-Saxton algorithm to enforce complex-amplitude profiles at the focal plane of the metasurface and to optimize the uniformity of the traps across the array. We fabricated and measured c-SOS metasurfaces that convert a Gaussian laser beam into arrays of bright traps, dark traps, and interleaved bright/dark traps.

Gerchberg-Saxton↗

Data and scripts associated with a manuscript investigating dissolved organic matter and microbial community linkages across seven globally distributed rivers

This data package is associated with the publication “Meta-metabolome ecology reveals that geochemistry and microbial functional potential are linked to organic matter development across seven rivers” submitted to Science of the Total Environment. This data package includes the data necessary to replicate the analyses presented within the manuscript to investigate dissolved organic matter (DOM) development across broad spatial distances and within divergent biomes. Specifically, we included the Fourier transform ion cyclotron mass spectrometry (FTICR-MS) data, geochemistry data, annotated metagenomic data, and results from ecological null modeling analyses in this data package. Additionally, we included the scripts necessary to generate the figures from the manuscript. Complete metagenomic data associated with this data package can be found at the National Center for Biotechnology (NCBI) under Bioproject PRJNA946291. This dataset consists of (1) four folders; (2) a file-level metadata (flmd) file; (3) a data dictionary (dd) file; (4) a factor sheet describing samples; and (5) a readme. The FTICR Data folder contains (1) the processed Fourier transform ion cyclotron mass spectrometry (FTICR-MS) data; (2) a transformation-weighted characteristics dendrogram generated from the FTICR-MS data; and (3) the script used to generate all FTICR-MS related figures. The Geochemical Data folder contains (1) the single geochemistry data file and (2) the R script responsible for generating associated figures. The Metagenomic Data folder contains (1) annotation information across different levels; (2) carbohydrate active enzyme (CAZyme) information from the dbCAN database (Yin et al., 2012); (3) phylogenetic tree data (FASTAs, alignments, and tree file); and (4) the scripts necessary to analyze all of these data and generate figures. The Null Modeling Data folder contains (1) data generated during null modeling for each river and all rivers combined and (2) the R scripts necessary to process the data. All files are .csv, .pdf, .tsv, .tre, .faa, .afa, .tree, or .R.

54 ENVIRONMENTAL SCIENCES↗

An Integral Activity-Based Protein Profiling Method for Higher Throughput Determination of Protein Target Sensitivity to Small Molecules

Activity-based protein profiling (ABPP) is a chemoproteomic technique that uses small molecule probes to label active enzymes selectively and covalently in complex proteomes. Competitive ABPP, which involves treatment of the active proteome with an analyte of interest, is especially powerful for profiling how small molecules impact specific protein activities. Advances in higher throughput workflows have made it possible to generate extensive competitive ABPP data across diverse biological samples, making this approach highly appealing for characterizing shared and unique proteins affected by perturbations such as drug or chemical exposures. To use the competitive ABPP approach effectively to understand potential adverse effects of chemicals of concern (CoC), a wide range of concentrations may be needed, particularly for chemicals that lack potency or toxicity data. In this work, we present an integral competitive ABPP method that enables target sensitivity determination for different organophosphate (OP) pesticides as model toxicants. Using previously developed OP-ABPs, we optimized conditions for tandem mass tag (TMT) multiplexing of ABPP samples and compared conventional competitive ABPP involving samples at discrete paraoxon concentrations to pooled samples across that same concentration range. We then expanded our approach to compare protein target sensitivities toward two additional OP pesticides, chlorpyrifos oxon and malaoxon. The results showed that differences in integral intensities for the pooled competition sample can be used to evaluate the relative sensitivity of specific proteins without increasing the overall number of samples. For 8 CoC concentrations of interest, this strategy reduced the number of TMT plexes and the corresponding number of LC–MS/MS analyses 3-fold. In conclusion, we envision the integral ABPP (IABPP) method will provide a means to screen diverse chemicals more rapidly to identify both high and low sensitivity protein targets.

activity-based probes↗

Aeroacoustic Assessment of Wind Plant Controls

The Aeroacoustic Assessment project aims to quantify changes in aeroacoustic noise generation by a utility scale wind turbine operating under imposed yaw offsets common for wake steering and wind plant control strategies. Active plant control utilizing wake deflection control strategies have been shown experimentally and computationally to reliably produce 1-2% of additional annual energy production (AEP) without significant changes in turbine structural loads, the potential impact on aeroacoustic emissions has yet to be quantified or completely understood. Yawed operation of a wind turbine changes the three-dimensional aerodynamic interaction between the rotor blades and the incoming atmospheric flow, leading to changes in noise generation. This work quantifies the extent to which active control induces additional aeroacoustic emissions from additional separation and other flow interaction dynamic effects. Given public concerns about wind turbine noise and the need for observational data required for regulators to establish noise restrictions, we must understand potential acoustic emissions resulting from active control prior to commercial deployment and the development of practical noise reduction methods and technologies. The work outlined in this report details the new aeroacoustic measurement capability developed at NREL and its application to making full-field observations of noise from a utility-scale wind turbine. Preliminary noise modeling with the aeroacoustics module in OpenFAST helped to establish the design of the experiment, specifically targeting the noise observed at observers distributed around the DOE-owned GE 1.5 MW wind turbine. Low-frequency and infrasound measurement capability implemented in this project establish an operational baseline for the wind turbine, setting the stage for future control, rotor blade, and turbine design research.

17 WIND ENERGY↗

Electrolytically Assisted Surface Decontamination (EASD{sup TM}) for POCO Operations - 20282

NNL in collaboration with C-Tech Innovation Ltd and Sellafield Ltd has been exploring innovative technologies to enable a significant reduction of radiological hazards within facilities during the Post Operational Clean Out (POCO) phase of a nuclear plant's life cycle. Reducing the hazard by effectively decontaminating plants in-situ during POCO delivers huge cost reductions for future decommissioning operations. These cost reduction benefits are realized by reducing the number and complexity of remote operations as well as lowering the long-term waste disposal costs. Whilst chemical decontamination can achieve the desired level of decontamination, applying aggressive chemical reagents is hazardous, potentially difficult to control and requires there to be complimentary effluent treatment and waste routes. This work has aimed to develop flexible and controllable decontamination processes which could be operated without the additional complexity and issues associated with chemical decontamination. The processes needed to be relatively fast and effective to minimize the time operators would spend in an active area. In addition, there was a driver to produce decontamination methodologies which generated a secondary waste compatible with current routes and which takes advantage of current waste capacity. The strategy therefore was to come up with a solution that works with, rather than against, the science and engineering behind process plants at Sellafield. Electrolytically Assisted Surface Decontamination (EASD{sup TM}) is an innovative electrochemical decontamination process (developed by NNL and C-Tech Innovation Ltd) that can remove activity from contaminated metal in very short time periods. Application of the patented electric waveform to the surface when treating contaminated metal with nitric acid has been shown to significantly enhance the decontamination performance. When compared to proposed baseline washout procedures at Sellafield, the only change to the process is the applied electrical waveform which is temporary and controllable. The current causes dissolution of the metal surface being decontaminated which leads to activity transferring from the plant item into the nitric acid effluent stream. This innovation has the potential to transform the POCO process and allow a nitric acid based washout approach to deliver POCO quickly and cost effectively within the existing infrastructure. Several devices have now been designed that incorporate this EASD{sup TM} technology and enable the decontamination process to be applied to a range items commonly identified as being contaminated during nuclear decommissioning programmes such as pipework, tanks and hotspots of walls/floors. Inactive and active laboratory-scale testing has been completed using both simulated and 'real-life' contaminated (low level waste) metallic items retrieved from different nuclear sites. Active trials demonstrated that contaminated items could be treated to free release levels within minutes. Engineering scale tests are currently being performed, with guidance from Sellafield's system engineers and plant managers, to provide the necessary re-assurance the designed devices could be successfully deployed in an on-plant scenario. The final stage of this development work is to carry out an active demonstration of the decontamination technology on Thorp at Sellafield. This paper aims to highlight progress made to date with the EASD{sup TM} technology and, more specifically, the development of an in-situ decontamination device for deployment within radioactive pipework. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Data-Driven Template Discovery Using Graph Convolutional Neural Networks

Modeling adversarial activities is a critical component of developing high-con?dence indicators of efforts to acquire, fabricate, proliferate, and/or deploy weapons of mass terror (WMTs). Current approaches to generating representative patterns of interest (a.k.a templates) from the real-world domains involve a Subject Matter Expert (SME)-guided manual process. The goal of Data-Driven Template Discovery (DDTD) is to use a (potentially small) set of SME generated templates to discover other previously unknown and interesting templates in an attributed graph. A template is an activity pattern describing a set of interactions among a group of nodes in the graph. The motivation behind DDTD is to expand the original set of templates, without having SMEs craft all the templates by hand. DDTD also provides seed templates to SMEs, to help them construct larger, high-?delity, and scenario-oriented templates. In these cases, obtaining a larger set of templates that are related (contain similar signals) to the original set is of great value. In this work, we propose to use Graph Convolutional Neural Networks (GCNs) to discover new templates that are heavily related to the original set. GCNs are a family of Neural Network (NN) architectures especially designed to work directly on graphs. In contrast to the traditional NNs, that require considerable amounts of labeled data, GCNs do not require a big labeled training set because they can directly leverage the graph structure instead. This property makes GCNs the perfect tool for creating activity templates.

Joaristi, Mikel↗

Can the Solar Atmosphere Generate Very-High-Energy Cosmic Rays?

The origin and acceleration of high-energy particles, constituting cosmic rays, is likely to remain an important topic in modern astrophysics. Among the two categories galactic and solar cosmic rays, the latter are much less investigated. The primary source of solar cosmic ray particles are impulsive explosions of the magnetized plasma, known as solar flares and coronal mass ejections. These particles, however, are characterized by relatively low energies compared to their galactic counterparts. In this work, we explore the resonance wave–wave (RWW) interaction between the polarized electromagnetic radiation emitted by the solar active regions and the quantum waves associated with high-energy, relativistic electrons generated during solar flares. Mathematically, the RWW interaction problem boils down to analyzing a Klein–Gordon Equation (spinless electrons) embedded in the electromagnetic field. We find that RWW could accelerate the relativistic electrons to enormous energies even comparable to energies in the galactic cosmic rays.

acceleration of particles↗

The Role of Oxygen Transfer in Oxide Heterostructures on Functional Properties

A variety of mechanisms are reported to play critical roles in contributing to the high carrier/electron mobility in oxide/SrTiO 3 (STO) heterostructures. By using La 0.95 Sr 0.05 TiO 3 (LSTO) epitaxially grown on different single crystal substrates (such as STO, GdScO 3 , LaAlO 3 , (LaAlO 3 ) 0.3 (Sr 2 AlTaO 6 ) 0.7 , and CeO 2 buffered STO) as the model systems, the formation of a conducting substrate surface layer (CSSL) on STO substrate is shown at relatively low growth temperature and high oxygen pressure (725 °C, 5 × 10 –4 Torr), which contributes to the enhanced conductivity of the LSTO/STO heterostructures. Different from the conventional oxygen vacancy model, this work reveals that the formation of the CSSL occurs when growing an oxide layer (LSTO in this case) on STO, while neither annealing nor the growth of an Au layer alone at the exact same growth condition generates the CSSL in STO. It demonstrates that the oxide layer actively pulls oxygen from STO substrate at given growth conditions, leading to the formation of the CSSL. Here, the observations emphasize the oxygen transfer across film/substrate interface during the synthesis of oxide heterostructures playing a critical role in functional properties.

36 MATERIALS SCIENCE↗

Disruption of adenosine 2A receptor improves the anti-tumor function of anti-mesothelin CAR T cells both in vitro and in vivo

Chimeric antigen receptor (CAR) T cells have been successfully used for the treatment of hematological malignancies including acute and chronic lymphoblastic leukemia. However, results of CAR T cell projects in solid tumors have been less impressive to date, partly because of immunosuppressive tumor microenvironment (TME). It is widely known that high adenosine production is an important factor causing tumor-induced immunosuppression in TME, and adenosine mediates the suppression of anti-tumor T cell responses via binding and signaling through adenosine 2a receptor (A2aR). Previous studies have shown that adenosine generated by cancer cells significantly inhibits T cell anti-tumor activity through binding and then activating adenosine 2A receptors (A2aRs) of T cells. Based on the previous work, in our study, we evaluated whether A2aR disruption by shRNA could enhance the anti-tumor function of anti-mesothelin (MSLN) CAR T cells both in vitro and in vivo. For this goal above, we used MSLN-positive human ovarian serous carcinoma cells (SKOV3) and human colon cancer cells (HCT116) as target cancer cells while MSLN-negative human ovarian cancer cells (ES2) as non-target cancer cells. We observed that targeting cell-intrinsic A2aR through shRNA overexpression caused significant A2aR disruption in CAR T cells and profoundly increased CAR T cell efficacy in both CAR T cell cytokine production and cytotoxicity towards MSLN-positive cancer cells in vitro. More importantly, in SKOV3 xenograft mouse models, anti-MSLN CAR-T cells significantly reduced the tumor burden compared with non-transduced T cells, and the anti-tumor activity of A2aR-disrupted anti-MSLN CAR-T cells was stronger than that of wild-type anti-MSLN CAR-T cells. Altogether, our study showed enhanced anti-tumor efficacy caused by shRNA-mediated A2aR disruption in anti-MSLN CAR T cells both in vitro and in vivo, which proved that shRNA-mediated modification of gene expression might be an excellent strategy for improving CAR T cell function in immunosuppressive tumor microenvironment (TME) and could potentially improve the outcome of treatment in clinical trials.

60 APPLIED LIFE SCIENCES↗