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NASA NTRS1996

Report on Alternative Devices to Pyrotechnics on Spacecraft

Pyrotechnics accomplish many functions on today's spacecraft, possessing minimum volume/weight, providing instantaneous operation on demand, and requiring little input energy. However, functional shock, safety, and overall system cost issues, combined with emergence and availability of new technologies question their continued use on space missions. Upon request from the National Aeronautics and Space Administration's (NASA) Program Management Council (PMC), Langley Research Center (LaRC) conducted a survey to identify and evaluate state-of-the-art non-explosively actuated (NEA) alternatives to pyrotechnics, identify NEA devices planned for NASA use, and investigate potential interagency cooperative efforts. In this study, over 135 organizations were contacted, including NASA field centers, Department of Defense (DOD) and other government laboratories, universities, and American and European industrial sources resulting in further detailed discussions with over half, and 18 face-to-face briefings. Unlike their single use pyrotechnic predecessors, NEA mechanisms are typically reusable or refurbishable, allowing flight of actual tested units. NEAs surveyed include spool-based devices, thermal knife, Fast Acting Shockless Separation Nut (FASSN), paraffin actuators, and shape memory alloy (SMA) devices (e.g., Frangibolt). The electro-mechanical spool, paraffin actuator and thermal knife are mature, flight proven technologies, while SMA devices have a limited flight history. There is a relationship between shock, input energy requirements, and mechanism functioning rate. Some devices (e.g., Frangibolt and spool based mechanisms) produce significant levels of functional shock. Paraffin, thermal knife, and SMA devices can provide gentle, shock-free release but cannot perform critically timed, simultaneous functions. The FASSN flywheel-nut release device possesses significant potential for reducing functional shock while activating nearly instantaneously. Specific study recommendations include: (1) development of NEA standards, specifically in areas of material characterization, functioning rates, and test methods; (2) a systems level approach to assure successful NEA technology application; and (3) further investigations into user needs, along with industry/government system-level real spacecraft cost benefit trade studies to determine NEA application foci and performance requirements. Additional survey observations reveal an industry and government desire to establish partnerships to investigate remaining unknowns and formulate NEA standards, specifically those driven by SMAs. Finally, there is increased interest and need to investigate alternative devices for such functions as stage/shroud separation and high pressure valving. This paper summarizes results of the NASA-LaRC survey of pyrotechnic alternatives. State of-the-art devices with their associated weight and cost savings are presented. Additionally, a comparison of functional shock characteristics of several devices are shown, and potentially related technology developments are highlighted.

Lucy, M. H.↗

NASA NTRS1998

Adaptive Variable Bias Magnetic Bearing Control

Most magnetic bearing control schemes use a bias current with a superimposed control current to linearize the relationship between the control current and the force it delivers. With the existence of the bias current, even in no load conditions, there is always some power consumption. In aerospace applications, power consumption becomes an important concern. In response to this concern, an alternative magnetic bearing control method, called Adaptive Variable Bias Control (AVBC), has been developed and its performance examined. The AVBC operates primarily as a proportional-derivative controller with a relatively slow, bias current dependent, time-varying gain. The AVBC is shown to reduce electrical power loss, be nominally stable, and provide control performance similar to conventional bias control. Analytical, computer simulation, and experimental results are presented in this paper.

Johnson, Dexter↗

NASA NTRS2001

Unshrouded Centrifugal Turbopump Impeller Design Methodology

Turbopump weight continues to be a dominant parameter in the trade space for reduction of engine weight. Space Shuttle Main Engine weight distribution indicates that the turbomachinery make up approximately 30% of the total engine weight. Weight reduction can be achieved through the reduction of envelope of the turbopump. Reduction in envelope relates to an increase in turbopump speed and an increase in impeller head coefficient. Speed can be increased until suction performance limits are achieved on the pump or due to alternate constraints the turbine or bearings limit speed. Once the speed of the turbopump is set the impeller tip speed sets the minimum head coefficient of the machine. To reduce impeller diameter the head coefficient must be increased. A significant limitation with increasing head coefficient is that the slope of the head-flow characteristic is affected and this can limit engine throttling range. Unshrouded impellers offer a design option for increased turbopump speed without increasing the impeller head coefficient. However, there are several issues with regard to using an unshrouded impeller: there is a pump performance penalty due to the front open face recirculation flow, there is a potential pump axial thrust problem from the unbalanced front open face and the back shroud face, and since test data is very limited for this configuration, there is uncertainty in the magnitude and phase of the rotordynamic forces due to the front impeller passage. The purpose of the paper is to discuss the design of an unshrouded impeller and to examine the hydrodynamic performance, axial thrust, and rotordynamic performance. The design methodology will also be discussed. This work will help provide some guidelines for unshrouded impeller design.

Prueger, George H.↗

NASA NTRS2002

Structural Life and Reliability Metrics: Benchmarking and Verification of Probabilistic Life Prediction Codes

Over the past two decades there has been considerable effort by NASA Glenn and others to develop probabilistic codes to predict with reasonable engineering certainty the life and reliability of critical components in rotating machinery and, more specifically, in the rotating sections of airbreathing and rocket engines. These codes have, to a very limited extent, been verified with relatively small bench rig type specimens under uniaxial loading. Because of the small and very narrow database the acceptance of these codes within the aerospace community has been limited. An alternate approach to generating statistically significant data under complex loading and environments simulating aircraft and rocket engine conditions is to obtain, catalog and statistically analyze actual field data. End users of the engines, such as commercial airlines and the military, record and store operational and maintenance information. This presentation describes a cooperative program between the NASA GRC, United Airlines, USAF Wright Laboratory, U.S. Army Research Laboratory and Australian Aeronautical & Maritime Research Laboratory to obtain and analyze these airline data for selected components such as blades, disks and combustors. These airline data will be used to benchmark and compare existing life prediction codes.

Litt, Jonathan S.↗

NASA NTRS2003

120-GHz HEMT Oscillator With Surface-Wave-Assisted Antenna

Two monolithic microwave integrated circuits (MMICs) have been designed and built to function together as a source of electromagnetic radiation at a frequency of 120 GHz. One of the MMICs is an oscillator and is the highest-power 120-GHz oscillator reported thus far in the literature. The other MMIC is an end-fire antenna that radiates the oscillator signal. Although these MMICs were constructed as separate units and electrically connected with wire bonds, future oscillator/ antenna combinations could readily be fabricated as monolithic integrated units. Such units could be used as relatively high-power solid-state microwave sources in diverse applications that include automotive radar, imaging, scientific instrumentation, communications, and radio astronomy. As such, these units would be attractive alternatives to vacuum-tube oscillators, which are still used to obtain acceptably high power in the frequency range of interest. The oscillator (see figure) includes a high-electron-mobility transistor (HEMT), with gate-periphery dimensions of 4 by 37 m, in a common-source configuration. The series feedback element of the oscillator is a grounded coplanar waveguide (CPW) at the source. The HEMT is biased for class-A operation (meaning that current is conducted throughout the oscillation cycle) to maximize the output power of the oscillator. Input and output impedance-matching circuit elements are designed to maximize output power and to establish the conditions needed for oscillation. The design of the antenna takes advantage of surface waves, which, heretofore, have been regarded as highly disadvantageous because they can leak power and degrade the performances of antennas that have not been designed to exploit them. Measures taken to suppress surface waves have included complex machining of circuit substrates and addition of separate substrates. These measures are difficult to implement in standard MMIC fabrication processes. In contrast, because the design of the present antenna eliminates the need to suppress surface waves, the fabrication of the antenna is fully compatible with standard MMIC fabrication processes.

Samoska, Lorene↗

NASA NTRS2016

Experimental Evaluation of Equivalent-Fluid Models for Melamine Foam

Melamine foam is a soft porous material commonly used in noise control applications. Many models exist to represent porous materials at various levels of fidelity. This work focuses on rigid frame equivalent fluid models, which represent the foam as a fluid with a complex speed of sound and density. There are several empirical models available to determine these frequency dependent parameters based on an estimate of the material flow resistivity. Alternatively, these properties can be experimentally educed using an impedance tube setup. Since vibroacoustic models are generally sensitive to these properties, this paper assesses the accuracy of several empirical models relative to impedance tube measurements collected with melamine foam samples. Diffuse field sound absorption measurements collected using large test articles in a laboratory are also compared with absorption predictions determined using model-based and measured foam properties. Melamine foam slabs of various thicknesses are considered.

Allen, Albert R.↗

DOE OSTI2017

Overview and Systems Studies of Supercritical CO2 Power Cycles

<span>This seminar discusses both indirect and direct-fired supercritical CO2 (sCO2) power cycles, briefly reviews the status of pilot plants under development for each of these cycles, and discusses NETL’s systems studies of coal-fueled commercial-scale sCO2 plants with carbon capture and storage (CCS).  Indirect sCO2 systems studied include an oxy-fired circulating fluidized bed heat source coupled to various sCO2 power cycles.  The direct-fired sCO2 cycle design is thermally integrated with a Shell gasifier to efficiently burn syngas within the oxy-combustor of the sCO2 cycle.  The performance and cost analyses of these plants are discussed, as well as comparisons to alternative cycles with CCS.  Results show that coal-fueled sCO2 plants of either type can exceed 40% HHV plant efficiency with CCS, and have a reduced cost of electricity relative to other cycles.  Other cycle configurations that offer further improvements in plant performance and cost-effectiveness are also discussed.</span>

Weiland, Nathan↗

DOE OSTI2014

Electro-optically responsive composites of gold nanospheres in 5CB liquid crystal under direct current and alternating current joint action

Direct current (DC) electro-optical (EO) control of transmitted laser beam intensity based on EO controlled coherent light scattering and diffraction by stationary longitudinal texture pattern (LTP) is achieved in planar-oriented cells with a composite mixture of polymer-coated gold spherical nanoparticles (Au-NPs) with a mean diameter of about 12 nm and the room-temperature nematic pentylcyanobiphenyl (5CB). At relatively low DC voltage of about 5 V, the effective scattering/diffraction by Au-NPs/5CB composites leads to a spatial spreading of transmitted coherent light from a low-power continuous wave laser beam, resulting in a drastic reduction of its local intensity. The effect is polarization dependent and is strongest when the polarization of the input laser beam is along the LTP. The EO response of Au-NPs/5CB mixtures is studied under DC and alternating current (AC) joint action with the aim of the potential use of these composite materials as EO controlled diffusers. The specific V-shaped sharp dip in the DC voltage-dependent coherent light transmittance of Au-NPs/5CB planar films, as well as the possibility for erasing the scattering/diffractive LTP in the films by joint low AC voltage, can be useful for EO applications in the field of process control and for detection of weak dynamic electric fields.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

DOE OSTI2019

In-House Alternative for Chemical Analyses of Rhenium and Sulfur in Glass

Accurate measurements of rhenium (Re) and sulfur (S) concentrations in solid samples are of critical importance for the key research activities at the Pacific Northwest National Laboratory (PNNL) Waste Form Development Laboratory (WFDL) related to Re behavior during waste glass melting process and solubility of S in glass. Southwest Research Institute (SwRI) has provided reliable services for chemical analysis needs at WFDL; however, its long turnaround time, occasionally up to 5 months, has caused some difficulties. An in-house method was developed for dissolving and fusing glass and feed samples in preparation for analyses by inductively coupled plasma-optical emission spectrometry and -mass spectrometry at a PNNL facility. Using a previously developed sodium hydroxide fusion method as a basis, four groups of samples from Hanford waste glass research were digested and fused at WFDL. The samples included 1) Enhanced low-activity waste glass correlation phase 2/3 melter glasses from the Vitreous State Laboratory at the Catholic University of America, 2) AN-102 dried feeds and glasses, 3) SS-AN-102 dried feeds and glasses, and 4) Integrated Research Project S solubility study glasses. We evaluated three different sets of solution preparation and analysis combinations, which included 1) a WFDL-prepared solution analyzed at SwRI, 2) a PNNLprepared solution analyzed at a laboratory in the Building-331at PNNL, and 3) an SwRIprepared solution analyzed at SwRI. We concluded that the PNNL in-house Re results can be used in parallel with the SwRI data based on the relative standard deviation values less than 6% from three different sets of solution preparation and analysis for all three groups of rhenium-containing samples tested. However, it was proposed that the in-house S data be used for the barium oxide-free glasses only because of the issue of barium sulfate precipitation in digestion/fusion solutions prepared from glasses containing barium oxide. In addition, higher analytical biases between the PNNL and SwRI S results are expected compared to the Re results, based on the relative standard deviation values of less than 10% from three different sets of solution preparation and analysis for two groups of S-containing samples.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

NASA NTRS2019

Exploring Network-Related Optimization Problems Using Quantum Heuristics

Network-related connectivity optimization problems are underlying a wide range of applications and are also of high computational complexity. We consider studying network optimization problems using two types of quantum heuristics.One is quantum annealing, and the other Quantum Alternating Operator Ansatz, an extension of the Quantum Approximate Optimization Algorithms for gate-model quantum computation, in which a cost-function based unitary and a non-commuting mixing unitary are applied alternately. We present problem mappings for problems of finding the spanning-tree or spanning-graph of a graph that optimizes certain costs, and a variant that further requires the spanning-tree be degree-bounded. With quantum annealing, all constraints are cast into penalty terms in the cost Hamiltonian, and the solution is encoded as the ground state of the Hamiltonian. We provide three mappings to the quadratic unconstrained binary optimization (QUBO) form, compare the resource requirements, and analyze the tradeoffs. For QAOA, we give special focus on the design of mixers based on the constraints presented in the problem, such that the system evolution remains in a subspace of the full Hilbert space where all constraints are satisfied. In the spanning-tree problem, one such hard constraint is that a mixer applied to a spanning-tree needs also be a spanning tree. This involves checking the connectivity of a subgraph, which is a global condition common for most network-related problems. We show how this feature can be efficiently represented in the mixer in a quantum coherent way, based on manipulation of a descendant-matrix and an adjacent matrix. We further develop a mixer for the spanning-graphs based on the spanning-tree mixer.

Wang, Zhihui↗

DOE OSTI2016

Impact of Using Cross Sections Versus Recipes in Transition Fuel Cycle Analysis using ORION

ORION, a nuclear fuel cycle simulator developed at the UK National Nuclear Laboratory (NNL), is designed to simulate the operations of general nuclear fuel cycles, including once-through, limited recycle, and continuous recycle fuel cycle options. ORION can simulate the full range of nuclear-related facilities e.g. interim and long-term storage locations, fabrication and enrichment plants, reprocessing facilities, and reactors. It can track over 2,500 nuclides and can model decay and in-reactor irradiation. Based on ORION's ability to track the full isotopic mass flow between fuel cycle facilities (with or without decay), it is possible to model all of the necessary nuclide production and destruction routes. This is essential when calculating accurate spent nuclear fuel (SNF) compositions and associated metrics (e.g., decay heat and radioactivity). When modeling the transition from the current once through US fuel cycle to an alternative fuel cycle, it is important to accurately model the US pressurized water reactor (PWR) discharged SNF composition while minimizing the computational time. This paper discusses two rapid methods used to model the US PWR discharged SNF-fixed recipes versus cross sections-and it discusses the differences between the results from these two methods in relation to fuel cycle transition analysis. (authors)

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2024

Assessing Resilience in Lane Detection Methods: Infrastructure-Based Sensors and Traditional Approaches for Autonomous Vehicles

Traditional autonomous vehicle perception subsystems that use onboard sensors have the drawbacks of high computational load and data duplication. Infrastructure-based sensors, which can provide high quality information without the computational burden and data duplication, are an alternative to traditional autonomous vehicle perception subsystems. However, these technologies are still in the early stages of development and have not been extensively evaluated for lane detection system performance. Therefore, there is a lack of quantitative data on their performance relative to traditional perception methods, especially during hazardous scenarios, such as lane line occlusion, sensor failure, and environmental obstructions. We address this need by evaluating the influence of hazards on the resilience of three different lane detection methods in simulation: (1) traditional camera detection using a U-Net algorithm, (2) radar detections using infrastructure-based radar retro-reflectors (RRs), and (3) direct communication of lane line information using chip-enabled raised pavement markers (CERPMs). The performance of each of these methods is assessed using resilience engineering metrics by simulating the individual methods for each sensor technology’s response to related hazards in the CARLA simulator. Using simulation techniques to replicate these methods and hazards acquires extensive datasets without lengthy time investments. Specifically, the resilience triangle was used to quantitatively measure the resilience of the lane detection system to obtain unique insights into each of the three lane detection methods; notably the infrastructure-based CERPMs and RRs had high resistance to hazards and were not as easily affected as the vision-based U-Net. However, while U-Net was able to recover the fastest from the disruption as compared to the other two methods, it also had the most performance loss. Overall, this study demonstrates that while infrastructure-based lane keeping technologies are still in early development, they have great potential as alternatives to traditional ones.

Patil, Pritesh↗

DOE OSTI2026

Opportunities for bioenergy crops to support transitions from irrigated agriculture and conserve the U.S. High Plains Aquifer

This study investigates potential economic and groundwater driven transitions from irrigated maize production—the dominant irrigated cropping system in the High Plains Aquifer (HPA) region—to alternative crops such as sorghum and switchgrass, two common bioenergy feedstocks. Unsustainable groundwater extraction in the U.S. High Plains presents critical challenges including reduced irrigation capacities, diminished crop yields, lower land values, and escalating energy costs. Using a spatially explicit optimization framework combined with comprehensive economic and hydrogeological data, we evaluate optimal land-use strategies and irrigation system investments over a 30-year planning period. Results indicate significant regional variability in the future economic viability of irrigated agriculture, driven by differences in aquifer recharge rates, groundwater availability, and market conditions. Nebraska and parts of northern Texas can sustain irrigated maize profitability due to relatively favorable groundwater conditions and lower land rents, respectively. In contrast, many portions of Kansas and southern Texas are more likely to transition to dryland agriculture within two decades. Colorado and New Mexico show potential for significant adoption of switchgrass production as an alternative biomass-based energy crop. Overall, over the 30-year horizon, our model implies that approximately 23% of currently irrigated maize area across the HPA region may transition to dryland farming under business-as-usual conditions. This transition is complemented by a threefold increase in non-irrigated sorghum production, from 0.20 to 0.77 Mt yr−1, indicating that groundwater-driven shifts in agricultural production may support a larger regional base for bioenergy feedstocks. The study also reveals opportunities for producers to optimize economic returns and biomass production potential.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Deep Learning Scene Classification Experiments in Automatic Detection of Slums on Planetscope Imagery

Population growth is increasingly happening in slum settlements of the large urban centers in the Global South. The term "slum" encompasses a wide range of communities, located mostly in underserved areas, and often exhibiting distinct structural and functional informalities with a relatively high concentration of marginalized populations. To address the issues confronting slums for effective planning and development, including the realistic estimation of the resident population, identifying them accurately is fundamental. Given the disagreements over a universal definition, diverse characteristic features, and socio-political limitations, global detection of slums is a veritable challenge. In this paper, we present experiments in slum detection using a scene classification algorithm and 3-meter spatial resolution satellite imagery. We train and evaluate the model for slum detection in Mumbai, India for the year 2023 and test the temporal generalization of the trained model on Mumbai in 2020 and 2018. In addition, we explore the pathways toward geographic generalization to Kolkata and Delhi (India). We discuss several limitations in the workflow and model, situate our findings in the existing literature, and suggest improvements and alternatives. With this, we establish baseline methods and experiments as a first step towards developing an image-based global slum detection framework and algorithm. This work adds to the community discussion on methods, data challenges, and open questions related to the detection of slums globally. With this research, we hope to improve our understanding of human settlements, especially in critical areas, improve population estimates, and help measure progress towards the sustainable development goals.

Arndt, Jacob↗

DOE OSTI2022

Constellation's best estimate alternate source term methodology overview

Safety analyses for a nuclear power plants need to consider postulated accidents that results in at risk of accidental release of radiation. The regulations require plant specific safety analysis reports to include an evaluation of the requirements of 10CFR50.67. Such a safety analysis report mandates limits such that calculated radiological consequences relative to certain dose locations do not exceed a total effective dose equivalent (TEDE) limits following a postulated release of radioactivity. Calculations are performed to estimate the radiological consequences, in terms of dose, to people and equipment to ensure the estimated doses are within the prescribed limits. Analysis should demonstrate, with reasonable assurance, that these prescribed limits are complied with. Conventional methodologies utilize conservative approaches to address lack of uncertainty quantification in the utilized approaches, methods, and/or inputs. These built-in excess conservatisms often result in compounding effects and hence overly conservative results in the estimated radiological consequences, which leads to inaccurate margin evaluation for operation and accident mitigation. Therefore, evaluating accurate dose consequences is needed for both operational and safety reasons. The research documented in this paper provides an overview of Constellation's Best Estimate Alternate Source Term (BEAST) Methodology. BEAST methodology relies upon the use of realistic yet bounding input distributions for key analysis parameters, which replaces use of conservative deterministic singular inputs that bound overall analysis domain. This approach enables evaluating a more accurate accident analysis response, while enabling a bounding licensing basis envelope via more accurate quantification of uncertainty in the application. Therefore, built-in margin for a given scenario is more accurately evaluated.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2022

Construction of Nitrogen-abundant Graphyne Scaffolds via Mechanochemistry-Promoted Cross-Linking of Aromatic Nitriles with Carbide Toward Enhanced Energy Storage

The 2D graphyne-related scaffolds linked by carbon–carbon triple bonds have demonstrated promising applications in the field of catalysis and energy storage due to their unique features including high conductivity, permanent porosity, and electron-rich properties. However, the construction of related scaffolds is still mainly limited to the cross-linking of CaC 2 with multiple substituted aromatic halogens and there is still a lack of efficient methodology capable of introducing high-concentration heteroatoms within the architectures. The development of alternative and facile synthesis procedures to afford nitrogen-abundant graphyne materials is highly desirable yet challenging in the field of energy storage, particularly via the facile mechanochemical procedure under neat and ambient conditions. Here, in this study, graphyne materials with abundant nitrogen-containing species (nitrogen content of 6.9–29.3 wt.%), tunable surface areas (43–865 m 2 g -1 ), and hierarchical porosity are produced via the mechanochemistry-driven pathway by deploying highly electron-deficient multiple substituted aromatic nitriles as the precursors, which can undergo cross-linking reaction with CaC 2 to afford the desired nitrogen-doped graphyne scaffolds efficiently. Unique structural features of the as-synthesized materials contributed to promising performance in supercapacitor-related applications, delivering high capacitance of 254.5 F g -1 at 5 mV s -1 , attractive rate performance, and good long-term stability.

25 ENERGY STORAGE↗

DOE OSTI2013

Numerical stability of relativistic beam multidimensional PIC simulations employing the Esirkepov algorithm

Rapidly growing numerical instabilities routinely occur in multidimensional particle-in-cell computer simulations of plasma-based particle accelerators, astrophysical phenomena, and relativistic charged particle beams. Reducing instability growth to acceptable levels has necessitated higher resolution grids, high-order field solvers, current filtering, etc. except for certain ratios of the time step to the axial cell size, for which numerical growth rates and saturation levels are reduced substantially. This paper derives and solves the cold beam dispersion relation for numerical instabilities in multidimensional, relativistic, electromagnetic particle-in-cell programs employing either the standard or the Cole–Karkkainnen finite difference field solver on a staggered mesh and the common Esirkepov current-gathering algorithm. Good overall agreement is achieved with previously reported results of the WARP code. In particular, the existence of select time steps for which instabilities are minimized is explained. Additionally, an alternative field interpolation algorithm is proposed for which instabilities are almost completely eliminated for a particular time step in ultra-relativistic simulations.

43 PARTICLE ACCELERATORS↗

DOE OSTI2022

In vivo stabilization of a less toxic asparaginase variant leads to a durable antitumor response in acute leukemia

Asparagine is a non-essential amino acid since it can either be taken up via the diet or synthesized by asparagine synthetase. Acute lymphoblastic leukemia (ALL) cells do not express asparagine synthetase or express it only minimally, which makes them completely dependent on extracellular asparagine for their growth and survival. This dependency makes ALL cells vulnerable to treatment with L-asparaginase, an enzyme that hydrolyzes asparagine. To date, all clinically approved L-asparaginases have significant L-glutaminase co-activity, associated with non-immune related toxic side effects observed during therapy. Therefore, reduction of L-glutaminase co-activity with concomitant maintenance of its anticancer L-asparaginase effect may effectively improve the tolerability of this unique drug. Previously, we designed a new alternative variant of Erwinia chrysanthemi (ErA; Erwinaze) with decreased L-glutaminase co-activity, while maintaining its L-asparaginase activity, by the introduction of three key mutations around the active site (ErA-TM). However, Erwinaze and our ErA-TM variant have very short half-lives in vivo. Here, we show that the fusion of ErA-TM with an albumin binding domain (ABD)-tag significantly increases its in vivo persistence. In addition, we evaluated the in vivo therapeutic efficacy of ABD-ErA-TM in a B-ALL xenograft model of SUP-B15. Our results show a comparable long-lasting durable antileukemic effect between the standard-of-care pegylated-asparaginase and ABD-ErA-TM L-asparaginase, but with fewer co-glutaminase-related acute side effects. Since the toxic side effects of current L-asparaginases often result in treatment discontinuation in ALL patients, this novel ErA-TM variant with ultra-low L-glutaminase co-activity and long in vivo persistence may have great clinical potential.

60 APPLIED LIFE SCIENCES↗