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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.

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At least 1,387 records · Page 77
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Hardware Fuzzing with An Emulator

Bugs in digital logic have led to some significant security vulnerabilities. Hardware bugs are particularly troublesome since they cannot be easily patched. Additionally, if the bug is in the root of trust, all trust built upon it can be vulnerable. Traditional testing either require a deep knowledge of the system, creative attack vectors and lots of human interaction. This is not scalable as there are very few engineers that can wear the hat of a designer, a verification engineer, and a cybersecurity expert. Hardware fuzzing is a relatively new research area in dynamic hardware testing. It has proven to be an effective method for discovering bugs, unexpected behaviors, and security vulnerabilities in software. While hardware fuzzing is new to the hardware domain, it has a strong track record in software testing. Fuzzing is a testing technique that randomly mutates the input data to uncover bugs or vulnerabilities in the design. It is especially good at finding corner cases that test engineers can not envision. Another advantage over other dynamic testing techniques is that, if done well, deep knowledge of the design is not required. Additionally, fuzzing scales well. If the system is set up correctly, it can run unsupervised for weeks if necessary. In this work, we propose using hardware fuzzing to improve the input vector generation for an information flow tracking tool. To get reasonable throughput of test vectors, an emulator is targeted as the execution platform. Efficient emulator execution has some specific requirements.

42 ENGINEERING↗
DOE OSTI2024

Domesticating the green alga Scenedesmus obliquus

Microalgae cultivation processes exist only for a few species used in commercial applications. Their domestication is still in its infancy, with major advances required, specifically to overcome limiting factors in microalgae production. The goal is to develop superior strains without the need of genetic technologies that would require lengthy regulatory permits, and often limit consumer acceptance. Adaptive Laboratory Evolution techniques, alone or in conjunction with sexual recombination, can allow for rapid develop of improved strains and their industrial production. Approaches include increased photon utilization efficiency by cultures operating under full sunlight conditions due to higher light saturation levels, allowing for higher productivities under outdoor conditions. Decades of research yielded some promising results under controlled conditions with a few specific mutant strains. However, these failed to achieve the anticipated higher productivities in actual algal mass cultures, in part due to the inability of mutations to overcome photoinhibition, reactive oxygen species, and other pleiotropic impacts on photosynthesis.

09 BIOMASS FUELS↗
DOE OSTI2025

Enhancing Developer Productivity - L2 Milestone (Final Report)

This report documents the work done as part of the “Enhancing Developer Productivity” level 2 milestone. The team surveyed developers about impediments and successes; improved our CI pipeline monitoring and reporting; developed tools for line coverage reporting and analysis; improved compiler warning adherence in SIERRA; prototyped static analysis, AI, and mutation testing tooling in SIERRA; and developed a 3-5 year SIERRA plan document to help these initiatives continue past this milestone.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2026

Use of Digital Real-Time Simulation and Optimization to Identify Maximum Real Power Injection on Banshee Distribution Network

This study investigates the hosting capacity of the Banshee Distribution Network by optimizing the real power injection at carefully selected Distributed Energy Resource (DER) locations. The analysis is conducted within the framework of power system operational constraints, including bus voltage ranges, thermal line ratings, and transformer loading limits. A Python-based Genetic Algorithm (GA), implemented using the PyGAD library, is employed to iteratively identify the optimal power injection configuration that maximizes network utilization while preserving system reliability. The methodology integrates a real-time simulation environment using the Real-Time Digital Simulator (RTDS), allowing high-fidelity evaluation of power flow and voltage behavior under each proposed injection scenario. By coupling the optimization algorithm with real-time simulation feedback, this approach ensures that both static and dynamic constraints are enforced during the evaluation process. The GA leverages evolutionary operators such as selection, crossover, and mutation to navigate the nonlinear search space efficiently. The results of the study delineate the feasible hosting capacity at three targeted buses, reflecting maximum real power levels that can be injected without causing voltage violations, transformer overloading, or line congestion. These findings provide a decision- support tool for distribution planners and utilities aiming to integrate higher penetrations of DERs in existing infrastructure. Additionally, the work lays the foundation for extending such optimization techniques to multi-objective formulations, including economic dispatch and reactive power coordination, in future studies.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2023

Deletion of Carboxypeptidase E in β-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice

Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesity and hyperglycemia. We aimed to determine whether loss of Cpe in pancreatic β-cells disrupts proinsulin processing and accelerates development of diabetes and obesity in mice. Pancreatic β-cell–specific Cpe knockout mice (βCpeKO; Cpe fl/fl x Ins1 Cre/+ ) lack mature insulin granules and have elevated proinsulin in plasma; however, glucose-and KCl-stimulated insulin secretion in βCpeKO islets remained intact. High-fat diet–fed βCpeKO mice showed weight gain and glucose tolerance comparable with those of Wt littermates. Notably, β-cell area was increased in chow-fed βCpeKO mice and β-cell replication was elevated in βCpeKO islets. Transcriptomic analysis of βCpeKO β-cells revealed elevated glycolysis and Hif1α-target gene expression. On high glucose challenge, β-cells from βCpeKO mice showed reduced mitochondrial membrane potential, increased reactive oxygen species, reduced MafA, and elevated Aldh1a3 transcript levels. Following multiple low-dose streptozotocin injections, βCpeKO mice had accelerated development of hyperglycemia with reduced β-cell insulin and Glut2 expression. In conclusion, these findings suggest that Cpe and proper proinsulin processing are critical in maintaining β-cell function during the development of hyperglycemia.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Selecting Minimal Motion Primitive Libraries with Genetic Algorithms

Motion primitives allow for application of discrete search algorithms to rapidly produce trajectories in complex continuous space. The maneuver automaton (MA) provides an elegant formulation for creating a primitive library based on trims and maneuvers. However, performance is fundamentally limited by the contents of the primitive library. If the library is too sparse, performance can be poor in terms of path cost, whereas a library that is too large can increase run time. This work outlines new methods for using genetic algorithms to prune a primitive library. The proposed methods balance the path cost and planning time while maintaining the reachability of the MA. The genetic algorithm in this paper evaluates and mutates populations of motion primitive libraries to optimize both objectives. Here, we illustrate the performance of these methods with a simulated study using a nonlinear medium-fidelity F-16 model. We optimize a library with the presented algorithm for obstacle-free navigation and a nap-of-the-Earth navigation task. In the obstacle-free navigation task, we show a tradeoff of a 10.16% higher planning cost for a 96.63% improvement in run time. In the nap-of-the-Earth task, we show a tradeoff of a 9.712% higher planning cost for a 92.06% improvement in run time.

42 ENGINEERING↗
DOE OSTI2026

pACB112

For recombinant expression of fghA (PP_1617 from Pseudomonas putida) with the S11R mutation and a C-terminal His tag

Adaptive laboratory evolution↗
DOE OSTI2026

pACB113

For recombinant expression of fghA (PP_1617 from Pseudomonas putida) with the W15C mutation and a C-terminal His tag

Adaptive laboratory evolution↗
DOE OSTI2026

pACB120

For recombinant expression of fghA (PP_1617 from Pseudomonas putida) with five mutations (K10N, S11R, W15C, G76V, G258D) and a C-terminal His tag

Adaptive laboratory evolution↗
DOE OSTI2026

pACB143

For recombinant expression of vanB (PP_3737 from Pseudomonas putida) with the A24P mutation and an N-terminal thrombin-cleavable His tag

Adaptive laboratory evolution↗
DOE OSTI2022

Structure and conformational dynamics of Clostridioides difficile toxin A

Clostridioides difficile toxin A and B (TcdA and TcdB) are two major virulence factors responsible for diseases associated with C. difficile infection (CDI). Here, we report the 3.18-Å resolution crystal structure of a TcdA fragment (residues L843–T2481), which advances our understanding of the complete structure of TcdA holotoxin. Our structural analysis, together with complementary single molecule FRET and limited proteolysis studies, reveal that TcdA adopts a dynamic structure and its CROPs domain can sample a spectrum of open and closed conformations in a pH-dependent manner. Furthermore, a small globular subdomain (SGS) and the CROPs protect the pore-forming region of TcdA in the closed state at neutral pH, which could contribute to modulating the pH-dependent pore formation of TcdA. A rationally designed TcdA mutation that trapped the CROPs in the closed conformation showed drastically reduced cytotoxicity. Taken together, these studies shed new lights into the conformational dynamics of TcdA and its roles in TcdA intoxication.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Section-level genome sequencing and comparative genomics of Aspergillus sections Cavernicolus and Usti.

The genus Aspergillus is diverse, including species of industrial importance, human pathogens, plant pests, and model organisms. Aspergillus includes species from sections Usti and Cavernicolus, which until recently were joined in section Usti, but have now been proposed to be non-monophyletic and were split by section Nidulantes, Aenei and Raperi. To learn more about these sections, we have sequenced the genomes of 13 Aspergillus species from section Cavernicolus (A. cavernicola, A. californicus, and A. egyptiacus), section Usti (A. carlsbadensis, A. germanicus, A. granulosus, A. heterothallicus, A. insuetus, A. keveii, A. lucknowensis, A. pseudodeflectus and A. pseudoustus), and section Nidulantes (A. quadrilineatus, previously A. tetrazonus). We compared these genomes with 16 additional species from Aspergillus to explore their genetic diversity, based on their genome content, repeat-induced point mutations (RIPs), transposable elements, carbohydrate-active enzyme (CAZyme) profile, growth on plant polysaccharides, and secondary metabolite gene clusters (SMGCs). All analyses support the split of section Usti and provide additional insights: Analyses of genes found only in single species show that these constitute genes which appear to be involved in adaptation to new carbon sources, regulation to fit new niches, and bioactive compounds for competitive advantages, suggesting that these support species differentiation in Aspergillus species. Sections Usti and Cavernicolus have mainly unique SMGCs. Section Usti contains very large and information-rich genomes, an expansion partially driven by CAZymes, as section Usti contains the most CAZyme-rich species seen in genus Aspergillus. Section Usti is clearly an underutilized source of plant biomass degraders and shows great potential as industrial enzyme producers. Citation: Nybo JL, Vesth TC, Theobald S, Frisvad JC, Larsen TO, Kjaerboelling I, Rothschild-Mancinelli K, Lyhne EK, Barry K, Clum A, Yoshinaga Y, Ledsgaard L, Daum C, Lipzen A, Kuo A, Riley R, Mondo S, LaButti K, Haridas S, Pangalinan J, Salamov AA, Simmons BA, Magnuson JK, Chen J, Drula E, Henrissat B, Wiebenga A, Lubbers RJM, Müller A, dos Santos Gomes AC, Mäkelä MR, Stajich JE, Grigoriev IV, Mortensen UH, de Vries RP, Baker SE, Andersen MR (2025). Section-level genome sequencing and comparative genomics of Aspergillus sections Cavernicolus and Usti. Studies in Mycology 111: 101-114. doi: 10.3114/sim.2025.111.03.

59 BASIC BIOLOGICAL SCIENCES↗
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↗
DOE OSTI2021

Re-routing of Sugar Catabolism Provides a Better Insight Into Fungal Flexibility in Using Plant Biomass-Derived Monomers as Substrates

The filamentous ascomycete Aspergillus niger has received increasing interest as a cell factory, being able to efficiently degrade plant cell wall polysaccharides as well as having an extensive metabolism to convert the released monosaccharides into value added compounds. The pentoses D-xylose and L-arabinose are the most abundant monosaccharides in plant biomass after the hexose D-glucose, being major constituents of xylan, pectin and xyloglucan. In this study, the influence of selected pentose catabolic pathway (PCP) deletion strains on growth on plant biomass and re-routing of sugar catabolism was addressed to gain a better understanding of the flexibility of this fungus in using plant biomass-derived monomers. The transcriptome, metabolome and proteome response of three PCP mutant strains, Δ larA Δ xyrA Δ xyrB , Δ ladA Δ xdhA Δ sdhA and Δ xkiA , grown on wheat bran (WB) and sugar beet pulp (SBP), was evaluated. Our results showed that despite the absolute impact of these PCP mutations on pure pentose sugars, they are not as critical for growth of A. niger on more complex biomass substrates, such as WB and SBP. However, significant phenotypic variation was observed between the two biomass substrates, but also between the different PCP mutants. This shows that the high sugar heterogeneity of these substrates in combination with the high complexity and adaptability of the fungal sugar metabolism allow for activation of alternative strategies to support growth.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

An Innovative High Throughput Genome Releaser for Rapid and Efficient PCR Screening

High-throughput PCR screening is vital in synthetic biology and metabolic engineering as it allows researchers to rapidly analyze and detect numerous targeted genetic mutation in the genome. Current challenges for high-throughput PCR screening in synthetic biology include efficiently preparing genomic DNA, optimizing protocols for diverse sample types, managing contamination risks, and effectively analyzing the large volumes of data generated while ensuring consistent and accurate results. In this study, we present the development of a High Throughput Genome Releaser (HTGR), an innovative device addressing common challenges in screening PCR. This genome DNA releaser is designed based on a squash method for rapid, cost-effective, and efficient DNA release, optimized for subsequent PCR reactions. After experimenting with various synthetic materials, we selected a plastic that closely replicates the smooth surface and compression properties of microscope slides, ensuring reliable performance. We engineered a device featuring a 96-Well Plate and a shear applicator, operable both manually and automatically, and compatible with standard liquid-handling robot platform. This compatibility enhances ease of use in high-throughput PCR workflows. Additionally, we developed software to support its automatic functions. Our results demonstrated that the specially engineered 96-Well Plate and HTGR can effectively squash fungal spores , which release enough genome DNA for PCR screening. The genome releaser facilitates the preparation of PCR-amplifiable genomic DNA substrate from 96 samples within minutes, eliminates the need for extraction buffers, and is adaptable to a wide range of microorganisms and cells, which could significantly advance biomanufacturing processes.

Yuan, Guoliang [BATTELLE (PACIFIC NW LAB)]↗
DOE OSTI2022

A Novel DNA Repair Gene Signature for Immune Checkpoint Inhibitor-Based Therapy in Gastric Cancer

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Adaptive Phenotypic Plasticity Stabilizes Evolution in Fluctuating Environments

Fluctuating environmental conditions are ubiquitous in natural systems, and populations have evolved various strategies to cope with such fluctuations. The particular mechanisms that evolve profoundly influence subsequent evolutionary dynamics. One such mechanism is phenotypic plasticity, which is the ability of a single genotype to produce alternate phenotypes in an environmentally dependent context. Here, we use digital organisms (self-replicating computer programs) to investigate how adaptive phenotypic plasticity alters evolutionary dynamics and influences evolutionary outcomes in cyclically changing environments. Specifically, we examined the evolutionary histories of both plastic populations and non-plastic populations to ask: (1) Does adaptive plasticity promote or constrain evolutionary change? (2) Are plastic populations better able to evolve and then maintain novel traits? And (3), how does adaptive plasticity affect the potential for maladaptive alleles to accumulate in evolving genomes? We find that populations with adaptive phenotypic plasticity undergo less evolutionary change than non-plastic populations, which must rely on genetic variation from de novo mutations to continuously readapt to environmental fluctuations. Indeed, the non-plastic populations undergo more frequent selective sweeps and accumulate many more genetic changes. We find that the repeated selective sweeps in non-plastic populations drive the loss of beneficial traits and accumulation of maladaptive alleles, whereas phenotypic plasticity can stabilize populations against environmental fluctuations. This stabilization allows plastic populations to more easily retain novel adaptive traits than their non-plastic counterparts. In general, the evolution of adaptive phenotypic plasticity shifted evolutionary dynamics to be more similar to that of populations evolving in a static environment than to non-plastic populations evolving in an identical fluctuating environment. All natural environments subject populations to some form of change; our findings suggest that the stabilizing effect of phenotypic plasticity plays an important role in subsequent adaptive evolution.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

A Coarse-Grained Model of Affinity Maturation Indicates the Importance of B-Cell Receptor Avidity in Epitope Subdominance

The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal in the design of vaccines against rapidly-mutating viruses. In the case of influenza, many bnAbs that target conserved epitopes on the stem of the hemagglutinin protein (HA) have been discovered. However, these antibodies are rare, are not boosted well upon reinfection, and often have low neutralization potency, compared to strain-specific antibodies directed to the HA head. Different hypotheses have been proposed to explain this phenomenon. We use a coarse-grained computational model of the germinal center reaction to investigate how B-cell receptor binding valency affects the growth and affinity maturation of competing B-cells. We find that receptors that are unable to bind antigen bivalently, and also those that do not bind antigen cooperatively, have significantly slower rates of growth, memory B-cell production, and, under certain conditions, rates of affinity maturation. The corresponding B-cells are predicted to be outcompeted by B-cells that bind bivalently and cooperatively. We use the model to explore strategies for a universal influenza vaccine, e.g., how to boost the concentrations of the slower growing cross-reactive antibodies directed to the stem. The results suggest that, upon natural reinfections subsequent to vaccination, the protectiveness of such vaccines would erode, possibly requiring regular boosts. Collectively, our results strongly support the importance of bivalent antibody binding in immunodominance, and suggest guidelines for developing a universal influenza vaccine.

60 APPLIED LIFE SCIENCES↗