Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “human activity”

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 1,243 records · Page 69
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Combining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5

Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand-up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen. We modeled the F5/E1E2 binding interface and generated predictions for mutations to improve binding using a Rosetta-based approach and dTERMen, an informatics approach. The modeling was complicated by the fact that a high-resolution structure of F5 is not available and the H3 loop of F5 exceeds the length for which current modeling approaches can determine a unique structure. A subset of the predicted mutations from both methods were incorporated into a phage display library of scFvs. This library and a library generated by error-prone PCR were screened for binding affinity to the recombinant antigen. Results from the screens identified favorable mutations which were incorporated into 12 human-IgG1 variants. The best variant, containing eight mutations, improved KD from 0.63 nM (parental) to 0.01 nM. While this did not improve neutralization or therapeutic potency of F5 against IAB, it did increase cross-reactivity to other closely related VEEV epizootic and enzootic strains, demonstrating the potential of this method to rapidly adapt existing therapeutics to emerging viral strains.

affinity-maturation↗
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 OSTI2023

tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut

Protein translation is orchestrated through tRNA aminoacylation and ribosomal elongation. Among the highly conserved structure of tRNAs, they have distinguishing features which promote interaction with their cognate aminoacyl tRNA synthetase (aaRS). These key features are referred to as identity elements. In our study, we investigated the tRNA:aaRS pair that installs the 22nd amino acid, pyrrolysine (tRNAPyl:PylRS). Pyrrolysyl-tRNA synthetases (PylRSs) are naturally encoded in some archaeal and bacterial genomes to acylate tRNAPyl with pyrrolysine. Their large amino acid binding pocket and poor recognition of the tRNA anticodon have been instrumental in incorporating > 200 noncanonical amino acids. PylRS enzymes can be divided into three classes based on their genomic structure. Two classes contain both an N-terminal and C-terminal domain, however the third class (ΔpylSn) lacks the N-terminal domain. In this study we explored the tRNA identity elements for a ΔpylSn tRNAPyl from Candidatus Methanomethylophilus alvus which drives the orthogonality seen with its cognate PylRS (MaPylRS). From aminoacylation and translation assays we identified five key elements in ΔpylSn tRNAPyl necessary for MaPylRS activity. The absence of a base (position 8) and a G–U wobble pair (G28:U42) were found to affect the high-resolution structure of the tRNA, while molecular dynamic simulations led us to acknowledge the rigidity imparted from the G–C base pairs (G3:C70 and G5:C68).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Safety in Artificial Intelligence: Challenges and Opportunities for the U.S. National Labs and Beyond

This report discusses the importance of the critical and underexplored topic of artificial intelligence (AI) safety, as highlighted during the “Strategy Alignment on AI Safety” workshop convened at Lawrence Livermore National Laboratory (LLNL) in April 2024. Through a summary of keynote talks, panel discussions, and breakout sessions, world-leading AI safety experts from academic, industry, national labs, and government agencies clearly agree on the need for and importance of large-scale investments for research and capabilities in AI safety. With the field innovating at unprecedented rates, there is increasing urgency to develop novel evaluation methodologies that allow full considerations of risks/threats of AI technologies in different domains. Quantitative metrics and effective methodologies that can evaluate and audit the “safeness” of how a given AI technology is trained, deployed, or regulated are, at best, nascent for certain scenarios or, more commonly, nonexistent. This maturation gap presents the possibility of serious threats to national security, and further inaction may have serious consequences. Additionally, the gap between the public’s and research community’s perceptions of AI risks/rewards is significant. While numerous voices from the AI community have expressed concern that the risks could be so high that future AI systems could inflict extinction-level damage to humanity if deployed incorrectly, the public largely is aware only of risk in low-impact scenarios. This discrepancy highlights the crucial need for researchers to articulate to governmental bodies what, why, and when various AI risks matter as part of motivating funding requests. Thus, the call to action for this community is to pursue AI safety as a “Big Science” project on a scale comparable to the Manhattan Project. High risks and high payoffs are on the table, but safe AI is a fast-moving target, and large-scale investments are needed to guide development of this technology in a responsible way. We highlight the need for a multilayered solution combining the development of new methods and algorithmic approaches to mitigate threats with an active participation of the government(s) in setting high industry standards and regulations based on state-of-the-art technology. The U.S. Department of Energy (DOE) national laboratories have served as leading institutions for scientific innovation in the U.S. for more than 70 years. Drawing on their expertise in the AI community and their history of safeguarding critical and sensitive information, and as we look to the future, national labs are the best choice for evaluating and safeguarding AI technologies.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Knockdown of DDX46 suppresses the proliferation and invasion of gastric cancer through inactivating Akt/GSK-3β/β-catenin pathway

DEAD-box RNA helicase 46 (DDX46) has recently been identified as a candidate oncogene in several types of human malignancies. To date, the role of DDX46 in gastric cancer has not been determined. The purpose of the current study was to explore the role of DDX46 in gastric cancer and the potential mechanism. DDX46-silecing or overexpressing gastric cancer cell lines were established to validate the role of DDX46. Our results showed that the expression of DDX46 was significantly increased in gastric cancer tissues and cell lines. Knockdown of DDX46 suppressed the proliferation and invasion of gastric cancer cells. Whereas, DDX46 overexpression enhanced the cell proliferation and invasion of gastric cancer cells. Furthermore, knockdown of DDX46 markedly suppressed the tumor growth of xenografts. Research into the mechanism revealed that DDX46 depletion inhibited the Akt/GSK-3β/β-catenin signaling pathway in gastric cancer cells. Notably, activation of Akt or β-catenin overexpression reversed the DDX46 depletion-mediated anti-cancer effect. In conclusion, these findings indicated that DDX46 exerted an oncogenic role in gastric cancer via regulating the Akt/GSK-3β/β-catenin signaling pathway. Thus, DDX46 might be utilized as a therapeutic anti-cancer target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Visualization and modeling of inhibition of IL-1β and TNF-α mRNA transcription at the single-cell level

Abstract IL-1β and TNF-α are canonical immune response mediators that play key regulatory roles in a wide range of inflammatory responses to both chronic and acute conditions. Here we employ an automated microscopy platform for the analysis of messenger RNA (mRNA) expression of IL-1β and TNF-α at the single-cell level. The amount of IL-1β and TNF-α mRNA expressed in a human monocytic leukemia cell line (THP-1) is visualized and counted using single-molecule fluorescent in-situ hybridization (smFISH) following exposure of the cells to lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria. We show that the small molecule inhibitors MG132 (a 26S proteasome inhibitor used to block NF-κB signaling) and U0126 (a MAPK Kinase inhibitor used to block CCAAT-enhancer-binding proteins C/EBP) successfully block IL-1β and TNF-α mRNA expression. Based upon this single-cell mRNA expression data, we screened 36 different mathematical models of gene expression, and found two similar models that capture the effects by which the drugs U0126 and MG132 affect the rates at which the genes transition into highly activated states. When their parameters were informed by the action of each drug independently, both models were able to predict the effects of the combined drug treatment. From our data and models, we postulate that IL-1β is activated by both NF-κB and C/EBP, while TNF-α is predominantly activated by NF-κB. Our combined single-cell experimental and modeling efforts show the interconnection between these two genes and demonstrates how the single-cell responses, including the distribution shapes, mean expression, and kinetics of gene expression, change with inhibition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Potent CRISPR-Cas9 inhibitors from Staphylococcus genomes

Anti-CRISPRs (Acrs) are small proteins that inhibit the RNA-guided DNA targeting activity of CRISPR-Cas enzymes. Encoded by bacteriophage and phage-derived bacterial genes, Acrs prevent CRISPR-mediated inhibition of phage infection and can also block CRISPR-Cas-mediated genome editing in eukaryotic cells. To identify Acrs capable of inhibiting Staphylococcus aureus Cas9 (SauCas9), an alternative to the most commonly used genome editing protein Streptococcus pyogenes Cas9 (SpyCas9), we used both self-targeting CRISPR screening and guilt-by-association genomic search strategies. Here we describe three potent inhibitors of SauCas9 that we name AcrIIA13, AcrIIA14, and AcrIIA15. These inhibitors share a conserved N-terminal sequence that is dispensable for DNA cleavage inhibition and have divergent C termini that are required in each case for inhibition of SauCas9-catalyzed DNA cleavage. In human cells, we observe robust inhibition of SauCas9-induced genome editing by AcrIIA13 and moderate inhibition by AcrIIA14 and AcrIIA15. We also find that the conserved N-terminal domain of AcrIIA13–AcrIIA15 binds to an inverted repeat sequence in the promoter of these Acr genes, consistent with its predicted helix-turn-helix DNA binding structure. These data demonstrate an effective strategy for Acr discovery and establish AcrIIA13–AcrIIA15 as unique bifunctional inhibitors of SauCas9.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Discovery of Marburg virus neutralizing antibodies from virus-naïve human antibody repertoires using large-scale structural predictions

Marburg virus (MARV) disease is lethal, with fatality rates up to 90%. Neutralizing antibodies (Abs) are promising drug candidates to prevent or treat the disease. Current efforts are focused in part on vaccine development to induce such MARV-neutralizing Abs. We analyzed the antibody repertoire from healthy unexposed and previously MARV-infected individuals to assess if naïve repertoires contain suitable precursor antibodies that could become neutralizing with a limited set of somatic mutations. Here, we computationally searched the human Ab variable gene repertoire for predicted structural homologs of the neutralizing Ab MR78 that is specific to the receptor binding site (RBS) of MARV glycoprotein (GP). Eight Ab heavy-chain complementarity determining region 3 (HCDR3) loops from MARV-naïve individuals and one from a previously MARV-infected individual were selected for testing as HCDR3 loop chimeras on the MR78 Ab framework. Three of these chimerized antibodies bound to MARV GP. We then tested a full-length native Ab heavy chain encoding the same 17-residue-long HCDR3 loop that bound to the MARV GP the best among the chimeric Abs tested. Despite only 57% amino acid sequence identity, the Ab from a MARV-naïve donor recognized MARV GP and possessed neutralizing activity against the virus. Crystallization of both chimeric and full-length native heavy chain-containing Abs provided structural insights into the mechanism of binding for these types of Abs. Our work suggests that the MARV GP RBS is a promising candidate for epitope-focused vaccine design to induce neutralizing Abs against MARV.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Sac1 links phosphoinositide turnover to cryptococcal virulence

Cryptococcus neoformans is an environmentally acquired fungal pathogen that causes over 140,000 deaths per year. Cryptococcal infection occurs when infectious particles are deposited into the lung, where they encounter host phagocytic cells. C. neoformans may be engulfed by these phagocytes, an important step of infection that leads to outcomes ranging from termination of infection to cryptococcal dissemination. To study this critical process, we screened approximately 4,700 cryptococcal gene deletion mutants for altered uptake, using primary mouse and human phagocytic cells. Among the hits of these two screens, we identified 93 mutants with perturbed uptake in both systems, as well as others with differences in uptake by only one cell type. We further screened the hits for changes in thickness of the capsule, a protective polysaccharide layer around the cell which is an important cryptococcal virulence factor. The combination of our three screens yielded 45 mutants, including one lacking the phosphatidylinositol-4-phosphate phosphatase Sac1. In this work, we implicate Sac1 in both host cell uptake and capsule production. We found that sac1 mutants exhibit lipid trafficking defects, reductions in secretory system function, and changes in capsule size and composition. Many of these changes occur specifically in tissue culture media, highlighting the role of Sac1 phosphatase activity in responding to the stress of host-like conditions. Overall, these findings show how genome-scale screening can identify cellular factors that contribute to our understanding of cryptococcal biology and demonstrate the role of Sac1 in determining fungal virulence.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance

Introduction Clinical use of several small molecule drugs may lead to severe T-cell-mediated idiosyncratic drug hypersensitivity reactions (iDHR) linked to HLA alleles, including abacavir (ABC) with HLA-B*57:01. Due to study limitations in humans, pathogenic networks in iDHR remain elusive. HLA transgenic murine models have been proposed to bridge knowledge gaps in tolerance and susceptibility to drugs. Methods Mice expressing HLA-B*57:01 and Foxp3-DTR/EGFP were generated to selectively deplete regulatory T-cells (Treg) with diphtheria toxin. ABC was administered for 8 days alone or together with cell- and cytokine-depleting antibodies. Cellular and transcriptomic responses were analyzed by RNA, flow cytometry and fluorescence methods. Results While CD8 + T-cell responses to ABC require HLA presentation, ABC also triggered mitochondrial stress in macrophagesin vitro, independently of HLA.In vivo, Treg were the primary mechanism of drug tolerance controlling HLA presentation and costimulation by antigen presenting cells. Treg ablation uncovered immune adverse events linked to activation and proliferation of both drug-specific and bystander CD8 + T-cells through CD28-mediated pathways with support from CD4 + non-Treg. Type-I interferon (IFN-I) and cellular-stress pathways influenced the fate of lymph node cells responding to ABC, implicating innate immune cells such as macrophages and plasmacytoid dendritic cells in the development of T-cell responses against the drug. IFN-I and IL-2 were necessary for CD8 + T-cell differentiation and ABC-induced adverse reactions. Conclusions This study unveils novel immune mechanisms driven by drug and host-related factors required forin vivoreactions and sheds light on potential biomarker and therapeutic targets for managing and preventing severe and life-threatening iDHR.

Immunology↗
DOE OSTI2024

Biomass Carbon Removal and Storage (BiCRS)

To achieve the ambitious net-zero emission goal by 2050, it is vital to explore practical approaches for removing carbon dioxide from the air. One promising method is Biomass Carbon Removal and Storage (BiCRS). BiCRS combines the natural ability of plants to convert carbon dioxide into biomass with human engineering to store the biomass, or derived products (char), belowground where it won't decompose. By securely storing these materials underground, we can trap the carbon dioxide absorbed by the plants during their growth, thus aiding in carbon removal from the atmosphere. BiCRS not only addresses carbon emissions but also has co-benefits such as wildfire risk reduction by utilizing forest residues. It is essential to establish best practices to ensure accurate measurements of net carbon dioxide removed by BiCRS for policymakers, businesses and communities. Presently, there is a lack of consistent methods for calculating these removals, considering variables like plant type, storage conditions, and conditions for converting the biomass to other products for storage like char. This project develops guidelines for monitoring and reporting BiCRS activities, offering a dependable framework for measuring carbon dioxide removal, enabling adoption of transparent BiCRS approaches for making significant contributions to reducing carbon dioxide levels in the atmosphere.

biomass carbon removal and storage↗
DOE OSTI2023

KEBLM: Knowledge-Enhanced Biomedical Language Models

Pretrained language models (PLMs) have demonstrated strong performance on many natural language processing (NLP) tasks. Despite their great success, these PLMs are typically pretrained only on unstructured free texts without leveraging existing structured knowledge bases that are readily available for many domains, especially scientific domains. As a result, these PLMs may not achieve satisfactory performance on knowledge-intensive tasks such as biomedical NLP. Comprehending a complex biomedical document without domain-specific knowledge is challenging, even for humans. Inspired by this observation, we propose a general framework for incorporating various types of domain knowledge from multiple sources into biomedical PLMs. We encode domain knowledge using lightweight adapter modules, bottleneck feed-forward networks that are inserted into different locations of a backbone PLM. For each knowledge source of interest, we pretrain an adapter module to capture the knowledge in a self-supervised way. We design a wide range of self-supervised objectives to accommodate diverse types of knowledge, ranging from entity relations to description sentences. Once a set of pretrained adapters is available, we employ fusion layers to combine the knowledge encoded within these adapters for downstream tasks. Each fusion layer is a parameterized mixer of the available trained adapters that can identify and activate the most useful adapters for a given input. Our method diverges from prior work by including a knowledge consolidation phase, during which we teach the fusion layers to effectively combine knowledge from both the original PLM and newly-acquired external knowledge using a large collection of unannotated texts. After the consolidation phase, the complete knowledge-enhanced model can be fine-tuned for any downstream task of interest to achieve optimal performance. Extensive experiments on many biomedical NLP datasets show that our proposed framework consistently improves the performance of the underlying PLMs on various downstream tasks such as natural language inference, question answering, and entity linking. These results demonstrate the benefits of using multiple sources of external knowledge to enhance PLMs and the effectiveness of the framework for incorporating knowledge into PLMs. Finally, while primarily focused on the biomedical domain in this work, our framework is highly adaptable and can be easily applied to other domains, such as the bioenergy sector.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗
DOE OSTI2024

Carbohydrate Deacetylase Unique to Gut Microbe Bacteroides Reveals Atypical Structure

Bacteroides are often the most abundant, commensal species in the gut microbiome of industrialized human populations. One of the most commonly detected species is Bacteroides ovatus. It has been linked to benefits like the suppression of intestinal inflammation but is also correlated with some autoimmune disorders, for example irritable bowel disorder (IBD). Bacterial cell surface carbohydrates, like capsular polysaccharides (CPS), may play a role in modulating these varied host interactions. Recent studies have begun to explore the diversity of CPS loci in Bacteroides; however, there is still much unknown. Here, we present structural and functional characterization of a putative polysaccharide deacetylase from Bacteroides ovatus (BoPDA) encoded in a CPS biosynthetic locus. We solved four high resolution crystal structures (1.36-1.56 Å) of the enzyme bound to divalent cations Co 2+ , Ni 2+ , Cu 2+ , or Zn 2+ and performed carbohydrate binding and deacetylase activity assays. Structural analysis of BoPDA revealed an atypical domain architecture that is unique to this enzyme, with a carbohydrate esterase 4 (CE4) superfamily catalytic domain inserted into a carbohydrate binding module (CBM). Additionally, BoPDA lacks the canonical CE4 His-His-Asp metal binding motif and our structures show it utilizes a noncanonical His-Asp dyad to bind metal ions. BoPDA is the first protein involved in CPS biosynthesis from B. ovatus to be characterized, furthering our understanding of significant biosynthetic processes in this medically relevant gut microbe.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Using Satellite‐Derived Fire Arrival Times for Coupled Wildfire‐Air Quality Simulations at Regional Scales of the 2020 California Wildfire Season

Abstract Wildfire frequency has increased in the Western US over recent decades, driven by climate change and a legacy of forest management practices. Consequently, human structures, health, and life are increasingly at risk due to wildfires. Furthermore, wildfire smoke presents a growing hazard for regional and national air quality. In response, many scientific tools have been developed to study and forecast wildfire behavior, or test interventions that may mitigate risk. In this study, we present a retrospective analysis of 1 month of the 2020 Northern California wildfire season, when many wildfires with varying environments and behavior impacted regional air quality. We simulated this period using a coupled numerical weather prediction model with online atmospheric chemistry, and compare two approaches to representing smoke emissions: an online fire spread model driven by remotely sensed fire arrival times and a biomass burning emissions inventory. First, we quantify the differences in smoke emissions and timing of fire activity, and characterize the subsequent impact on estimates of smoke emissions. Next, we compare the simulated smoke to surface observations and remotely sensed smoke; we find that despite differences in the simulated smoke surface concentrations, the two models achieve similar levels of accuracy. We present a detailed comparison between the performance and relative strengths of both approaches, and discuss potential refinements that could further improve future simulations of wildfire smoke. Finally, we characterize the interactions between smoke and meteorology during this event, and discuss the implications that increases in regional smoke may have on future meteorological conditions.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

On-the-fly closed-loop materials discovery via Bayesian active learning

Active learning—the field of machine learning (ML) dedicated to optimal experiment design—has played a part in science as far back as the 18th century when Laplace used it to guide his discovery of celestial mechanics. In this work, we focus a closed-loop, active learning-driven autonomous system on another major challenge, the discovery of advanced materials against the exceedingly complex synthesis-processes-structure-property landscape. We demonstrate an autonomous materials discovery methodology for functional inorganic compounds which allow scientists to fail smarter, learn faster, and spend less resources in their studies, while simultaneously improving trust in scientific results and machine learning tools. This robot science enables science-over-the-network, reducing the economic impact of scientists being physically separated from their labs. The real-time closed-loop, autonomous system for materials exploration and optimization (CAMEO) is implemented at the synchrotron beamline to accelerate the interconnected tasks of phase mapping and property optimization, with each cycle taking seconds to minutes. We also demonstrate an embodiment of human-machine interaction, where human-in-the-loop is called to play a contributing role within each cycle. This work has resulted in the discovery of a novel epitaxial nanocomposite phase-change memory material.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Autonomous Navigation and Control of UGVs' in Nuclear Power Plants - 20381

The purpose of the husky A200 ground robot is to autonomously navigate through the places where it is very hazardous for human beings to reach and operate, like nuclear power plants, chemical industries. The aim is to navigate the ground robot autonomously with an Arm mounted on the robot along with the different sensors as camera, and Lidar. The autonomous motion of the robot is controlled by the controller which uses path planner for trajectory generation of the robot. The mission planner uses the current position of the husky A200, given the way points of the initial and the destination it would extract a best possible route based on the current events provided using GMapping. The global reference frame is used for planning the way points. Creating the appropriate path and the actions required to follow the path are given by the motion planner. The motion planner depends on the active sensor data such as obstacles, lanes, based on the sensor data feasible path is generated. Feasibility of the path is determined by the dynamics of the husky and a series of points generated with certain velocity and acceleration profile. The controller adjusts the lateral, longitudinal and yaw motion of the husky to command the behaviors. The kinematic model is developed for kinematic motion of the husky and the dynamic model is developed for transient and steady state characteristics. The images and other type of data captured by the camera are processed through the computational framework used to build machine learning models. TensorFlow will be used for deep learning and to identify and classify different objects around the husky. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2024

Exploring Subsite Selectivity within Plasmodium vivax N -Myristoyltransferase Using Pyrazole-Derived Inhibitors

N-myristoyltransferase (NMT) is a promising antimalarial drug target. Despite biochemical similarities between Plasmodium vivax and human NMTs, our recent research demonstrated that high selectivity is achievable. Herein, we report PvNMT-inhibiting compounds aimed at identifying novel mechanisms of selectivity. Various functional groups are appended to a pyrazole moiety in the inhibitor to target a pocket formed beneath the peptide binding cleft. The inhibitor core group polarity, lipophilicity, and size are also varied to probe the water structure near a channel. Selectivity index values range from 0.8 to 125.3. Cocrystal structures of two selective compounds, determined at 1.97 and 2.43 Å, show that extensions bind the targeted pocket but with different stabilities. A bulky naphthalene moiety introduced into the core binds next to instead of displacing protein-bound waters, causing a shift in the inhibitor position and expanding the binding site. Our structure-activity data provide a conceptual foundation for guiding future inhibitor optimizations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

CD206 + Trem2 + macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice

Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve. To better understand molecular programs contributing to PTOA development or resolution, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell RNA sequencing of synovial joints in PTOA-susceptible C57BL/6J (B6) and PTOA-resistant MRL/MpJ (MRL) mice. We identified significant differences in monocyte and macrophage subpopulations between MRL and B6 joints. A potent myeloid-driven anti-inflammatory response was observed in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. Multiple CD206 + macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206 + macrophages also robustly expressed Trem2 , a receptor involved in inflammation and myeloid cell activation. These data suggest that the PTOA resistant MRL mouse strain displays an enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated M2 macrophages within the synovial tissue and joint space.

60 APPLIED LIFE SCIENCES↗