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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Identification of recG genetic interactions in Escherichia coli by transposon sequencing

ABSTRACT Maintaining the integrity of the genome is of utmost importance for cell division and propagation. In Escherichia coli , the RecG protein has been implicated in processing branched recombination intermediates during DNA repair processes, but the primary cellular role(s) of RecG and the repair pathways in which it acts have been difficult to define. To gain additional insight into RecG function, we employed transposon sequencing to identify recG genetic interactions and reveal complementary or redundant functions. The strongest hits from the screen were the dam , uvrD , rnhA , radA , and rep genes. The conditional importance of these five genes in cells lacking recG was confirmed using a plasmid-based assay, revealing synthetic lethal interactions for most double deletion strains. Several of the synthetic lethal gene combinations (with uvrD, rep, and radA , but not rnhA or dam ) were suppressed by deletion of recF or recO , indicating that their genetic relationships involved roles in post-replication gap repair. Additionally, loss of the RecG/SSB interaction phenocopied a recG deletion when combined with dam , uvrD , radA , or rnhA deletions but not with rep . The results reinforce the idea of RecG as a general genome guardian. RecG has at least two functions. It plays an important role in the resolution of joint molecules behind the fork, formed during post-replication gap repair. RecG is also required to suppress genome over-replication caused by unscheduled replication initiation at R-loops, at double-strand breaks caused by dam inactivation, and during replication termination. IMPORTANCE DNA damage and subsequent DNA repair processes are mutagenic in nature and an important driver of evolution in prokaryotes, including antibiotic resistance development. Genetic screening approaches, such as transposon sequencing (Tn-seq), have provided important new insights into gene function and genetic relationships. Here, we employed Tn-seq to gain insight into the function of the recG gene, which renders Escherichia coli cells moderately sensitive to a variety of DNA-damaging agents when they are absent. The reported recG genetic interactions can be used in combination with future screens to aid in a more complete reconstruction of DNA repair pathways in bacteria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

MLEC-Sim: A Simulator for Evaluating Multi-Level Erasure Coding

We present MLEC-Sim, a sophisticated simulator for Multi-Level Erasure Coding (MLEC), developed in approximately 13 KLOC. The simulator is engineered to analyze the impact of various system configurations and erasure coding policies on system durability and network overhead. It supports a comprehensive range of parameters including disk capacity, disk I/O bandwidth, failure rates, network bandwidth, and system scale, accommodating various erasure coding approaches such as Single-Level Erasure Coding (SLEC), Multi-Level Erasure Coding (MLEC), and Local Reconstruction Codes (LRC). MLEC-Sim provides support for multiple chunk placement policies, including clustered parity and declustered parity, and encompasses a variety of repair methods like Repair-ALL, Repair-FCO, Repair-HYB, and Repair-MIN. It is capable of simulating disk failures through a variety of means, including distribution-based or trace-based mechanisms, and can handle complex multi-level (de)clustered placements and repair processes. A key feature of MLEC-Sim is its adoption of the splitting simulation method for evaluating system durabilities at extremely high levels, which are challenging to assess with traditional simulation approaches. This feature allows for a detailed evaluation of system resilience under a range of conditions, aiding in the selection of appropriate erasure coding solutions for enhancing system durability. MLEC-Sim contributes to the field of data storage and reliability by providing a tool for the detailed evaluation of the durability and efficiency of erasure coding configurations, intended for use by researchers and practitioners in the design and optimization of storage systems.

Wang, Meng↗
DOE OSTI2023

Quantifying Uncertainty of Deep Reinforcement Learning Based Decision Making for Operations and Maintenance of Nuclear Power Plant

This paper summarizes research that integrates condition monitoring and prognostics with decision making for nuclear power plant operations and maintenance. As part of this research, we have developed an online asset management tool to help reduce life-cycle maintenance and repair costs. Using the latest advancements in condition monitoring, supply chain analytics, and deep reinforcement learning, we have created a predictive maintenance tool that can optimize the maintenance and spare-part management of a repairable nuclear system. To demonstrate these methods, preliminary studies were conducted on a simple, representative maintenance system undergoing a stochastic degradation process that requires repairs or replacement to continue operation. Through Monte Carlo simulations, we were able to reduce maintenance spending by approximately 50% compared to optimized, time-based maintenance strategies. Not only does the decision maker reduce the average life-cycle costs, it also minimizes the chance of high cost scenarios, lowering the variance of the expected cost distributions, and reducing overall financial risk. Furthermore, this work also studies the ability of the decision maker to handle various levels of noise from observation uncertainty. By introducing uncertainty into the decision-making process, we have quantified the robustness and resiliency of the decision maker, as well as identified necessary levels of observability to demonstrate cost effectiveness.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2026

Nondestructive Evaluation of Carbon Fiber Reinforced Polymers

The American Society of Mechanical Engineers Boiler and Pressure Vessel Code requires repair and replacement of safety-related piping materials to meet the original Construction Code; however, no construction criteria currently exist for carbon fiber reinforced polymer (CFRP) materials in the nuclear industry. Although nondestructive examination (NDE) techniques for cast and wrought ferritic and austenitic steels are well established, licensees are increasingly deploying novel materials such as CFRP for which assessment of the use of NDE is required, as the inspectability of such materials and the influence of manufacturing processes on inspectability remain insufficiently understood. To address these gaps, Pacific Northwest National Laboratory (PNNL) evaluated the fabrication of several CFRP repair mockups and the effectiveness of NDE methods to support regulatory review of CFRP repairs in nuclear power plant applications. Representative flat-plate mockups containing realistic fabrication defects were manufactured and inspected using manual and automated tap testing, dynamic response spectroscopy (DRS), and ultrasonic testing (UT). The study identified significant fabrication variability, particularly in controlling defect size and epoxy thickness, which strongly influenced defect detectability by NDE methods. Tap testing was effective for shallow defects in thin epoxy configurations but unreliable for thicker repairs and deeper flaws. DRS demonstrated higher sensitivity to dry spots but produced unconfirmed indications for thicker plates, requiring further validation. Conventional UT, particularly at 1.0 MHz, showed the strongest overall capability for detecting a range of defects, although performance degraded with increasing repair thickness and complexity. The results highlight the need to better define critical defect sizes, develop reliable mockup fabrication methods, and validate NDE methods needed to support CFRP repairs.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Mitigation for Removal of Building 01-103 in the Area 1 Subdock, Nevada National Security Site, Nye County, Nevada

Building 01-103, the Drill Bit Repair Building was originally recorded as SHPO Resource No. B18848 in 2020 during an architectural survey of the Area 1 Subdock (Collins et al. 2022). It was recommended individually eligible for listing in the NRHP under Criteria A and C and contributing to the significance of the Area 1 Subdock Historic District. The SHPO concurred with these determinations in a letter dated April 29, 2022 (Reed 2022). The Drill Bit Repair Building retains all seven aspects of integrity. The location, materials, workmanship, feeling, and association have not changed since its original construction. The design was modified slightly in 1996 with the addition of a removable and non-destructive chain-link fence. Nearby buildings 01-101 and 01-102 were removed (Collins and Menocal 2020) but the other buildings and storage yards remain. Therefore, the integrity of setting has been changed, but not to the degree that the building no longer conveys its significance (see Figures 4 and 5 for comparison). Building 01-103 was constructed in 1985 to coincide with the relocation of the Area 3 Subdock to Area 1. The design for the new Subdock provided a centralized cluster of buildings surrounded by two large storage yards. The buildings included administrative and engineering office space, warehouses, a radiograph building, and Building 01-103 as the drill bit maintenance and repair building, among others. The Drill Bit Repair Building was critical to the success of underground nuclear testing and is eligible under Criterion A for its contribution to broad patterns of history by maintaining specially designed equipment for underground nuclear testing at the NNSS. It is also eligible under Criterion C as it is the only recorded example of a facility built specifically for the maintenance of big-hole drill bits on the NNSS. As it retains both significance and integrity, it remains individually eligible under Criteria A and C. In addition to its individual significance, the Drill Bit Repair Building also contributes to the significance of the Area 1 Subdock Historic District as a representative of a big-hole drilling support facility necessary for underground nuclear testing. The building and the equipment therein were designed specifically for testing at the NNSS, where much of the early technology and methods for big-hole drilling were developed. Its removal will result in not only the demolition of a contributing element but also a change in the physical features of the district’s setting that contribute to its historic significance. The change in setting will diminish the district’s integrity. However, the district still contains numerous examples of other buildings constructed for the purpose of supporting big-hole drilling and remains eligible under Criteria A and C.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Cas9-induced large deletions and small indels are controlled in a convergent fashion

Repair of Cas9-induced double-stranded breaks results primarily in formation of small insertions and deletions (indels), but can also cause potentially harmful large deletions. While mechanisms leading to the creation of small indels are relatively well understood, very little is known about the origins of large deletions. Using a library of clonal NGS-validated mouse embryonic stem cells deficient for 32 DNA repair genes, we have shown that large deletion frequency increases in cells impaired for non-homologous end joining and decreases in cells deficient for the central resection gene Nbn and the microhomology-mediated end joining gene Polq. Across deficient clones, increase in large deletion frequency was closely correlated with the increase in the extent of microhomology and the size of small indels, implying a continuity of repair processes across different genomic scales. Furthermore, by targeting diverse genomic sites, we identified examples of repair processes that were highly locus-specific, discovering a role for exonuclease Trex1. Finally, we present evidence that indel sizes increase with the overall efficiency of Cas9 mutagenesis. These findings may have impact on both basic research and clinical use of CRISPR-Cas9, in particular in conjunction with repair pathway modulation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

DNA double-strand break movement in heterochromatin depends on the histone acetyltransferase dGcn5

Abstract Cells employ diverse strategies to repair double-strand breaks (DSBs), a dangerous form of DNA damage that threatens genome integrity. Eukaryotic nuclei consist of different chromatin environments, each displaying distinct molecular and biophysical properties that can significantly influence the DSB-repair process. DSBs arising in the compact and silenced heterochromatin domains have been found to move to the heterochromatin periphery in mouse and Drosophila to prevent aberrant recombination events. However, it is poorly understood how chromatin components, such as histone post-translational modifications, contribute to these DSB movements within heterochromatin. Using irradiation as well as locus-specific DSB induction in Drosophila tissues and cultured cells, we find enrichment of histone H3 lysine 9 acetylation (H3K9ac) at DSBs in heterochromatin but not euchromatin. We find this increase is mediated by the histone acetyltransferase dGcn5, which rapidly localizes to heterochromatic DSBs. Moreover, we demonstrate that in the absence of dGcn5, heterochromatic DSBs display impaired recruitment of the SUMO E3 ligase Nse2/Qjt and fail to relocate to the heterochromatin periphery to complete repair. In summary, our results reveal a previously unidentified role for dGcn5 and H3K9ac in heterochromatic DSB repair and underscore the importance of differential chromatin responses at heterochromatic and euchromatic DSBs to promote safe repair.

Biochemistry & Molecular Biology↗
DOE OSTI2021

Genomic reconstruction of fossil and living microorganisms in ancient Siberian permafrost

Abstract Background Total DNA (intracellular, iDNA and extracellular, eDNA) from ancient permafrost records the mixed genetic repository of the past and present microbial populations through geological time. Given the exceptional preservation of eDNA under perennial frozen conditions, typical metagenomic sequencing of total DNA precludes the discrimination between fossil and living microorganisms in ancient cryogenic environments. DNA repair protocols were combined with high throughput sequencing (HTS) of separate iDNA and eDNA fraction to reconstruct metagenome-assembled genomes (MAGs) from ancient microbial DNA entrapped in Siberian coastal permafrost. Results Despite the severe DNA damage in ancient permafrost, the coupling of DNA repair and HTS resulted in a total of 52 MAGs from sediments across a chronosequence (26–120 kyr). These MAGs were compared with those derived from the same samples but without utilizing DNA repair protocols. The MAGs from the youngest stratum showed minimal DNA damage and thus likely originated from viable, active microbial species. Many MAGs from the older and deeper sediment appear related to past aerobic microbial populations that had died upon freezing. MAGs from anaerobic lineages, including Asgard archaea, however exhibited minimal DNA damage and likely represent extant living microorganisms that have become adapted to the cryogenic and anoxic environments. The integration of aspartic acid racemization modeling and metaproteomics further constrained the metabolic status of the living microbial populations. Collectively, combining DNA repair protocols with HTS unveiled the adaptive strategies of microbes to long-term survivability in ancient permafrost. Conclusions Our results indicated that coupling of DNA repair protocols with simultaneous sequencing of iDNA and eDNA fractions enabled the assembly of MAGs from past and living microorganisms in ancient permafrost. The genomic reconstruction from the past and extant microbial populations expanded our understanding about the microbial successions and biogeochemical alterations from the past paleoenvironment to the present-day frozen state. Furthermore, we provided genomic insights into long-term survival mechanisms of microorganisms under cryogenic conditions through geological time. The combined strategies in this study can be extrapolated to examine other ancient non-permafrost environments and constrain the search for past and extant extraterrestrial life in permafrost and ice deposits on Mars.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Preclinical Risk Evaluation of Normal Tissue Injury With Novel Radiosensitizers

Genotoxic damage induced by radiation triggers a highly coordinated DNA damage response, and molecular inhibitors of key nodes within this complex response network can profoundly enhance the antitumor efficacy of radiation. This is especially true for drugs targeting the catalytic subunit of DNA-dependent protein kinase, which is a core component of the nonhomologous end-joining DNA repair pathway, and ataxia telangiectasia mutated, which coordinates cell cycle arrest, apoptosis, and DNA repair functionalities after radiation exposure. Unlike the more modest in vitro radiosensitizing effects seen with classic sensitizing agents such as cisplatin, 5-fluorouracil, or taxanes, DNA-dependent protein kinase or ataxia telangiectasia mutated inhibitors provide much more robust sensitizing effects in vitro, as might be anticipated from targeting these key DNA repair modulators. However, patients with homozygous inactivating mutations of ataxia telangiectasia mutated or mice with homozygous defects in DNA-dependent protein kinase (severe combined immunodeficiency) have profoundly enhanced acute normal tissue radiation reactions. Therefore, there is significant potential that the combination of small molecule inhibitors of these kinases with radiation could cause similar dose-limiting acute normal tissue toxicities. Similarly, although less understood, inhibition of these DNA repair response pathways could markedly increase the risk of late radiation toxicities. Because these potent radiosensitizers could be highly useful to improve local control of otherwise radiation-resistant tumors, understanding the potential for elevated risks of radiation injury is essential for optimizing therapeutic ratio and developing safe and informative clinical trials. In this review, we will discuss 2 straightforward models to assess the potential for enhanced mucosal toxicity in the oral cavity and small intestine established in our laboratories. We also will discuss similar strategies for evaluating potential drug–radiation interactions with regard to increased risks of debilitating late effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Structural basis for $\mathrm{APE1}$ processing $\mathrm{DNA}$ damage in the nucleosome

Genomic DNA is continually exposed to endogenous and exogenous factors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucleosomes, which present a barrier to accessing and effectively repairing DNA damage. The mechanisms by which DNA repair proteins overcome this barrier to repair DNA damage in the nucleosome and protect genomic stability is unknown. Here, we determine how the base excision repair (BER) endonuclease AP-endonuclease 1 (APE1) recognizes and cleaves DNA damage in the nucleosome. Kinetic assays determine that APE1 cleaves solvent-exposed AP sites in the nucleosome with 3-6 orders of magnitude higher efficiency than occluded AP sites. A cryo-electron microscopy structure of APE1 bound to a nucleosome containing a solvent-exposed AP site reveal that APE1 uses a DNA sculpting mechanism for AP site recognition, where APE1 bends the nucleosomal DNA to access the AP site. Notably, additional biochemical and structural characterization of occluded AP sites identify contacts between the nucleosomal DNA and histone octamer that prevent efficient processing of the AP site by APE1. These findings provide a rationale for the position-dependent activity of BER proteins in the nucleosome and suggests the ability of BER proteins to sculpt nucleosomal DNA drives efficient BER in chromatin.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Stable hypermutators revealed by the genomic landscape of genes involved in genome stability among yeast species

Mutator phenotypes are short-lived due to the rapid accumulation of deleterious mutations. Yet, recent observations reveal that certain fungi can undergo prolonged accelerated evolution after losing genes involved in DNA repair. Here, we surveyed 1,154 yeast genomes representing nearly all known yeast species of the subphylum Saccharomycotina (phylum Ascomycota) to examine the relationship between reduced gene repertoires broadly associated with genome stability functions (e.g., DNA repair, cell cycle) and elevated evolutionary rates. We identified three distantly related lineages—encompassing 12% of species—that had both the most streamlined sets of genes involved in genome stability (specifically DNA repair) and the highest evolutionary rates in the entire subphylum. Two of these “faster-evolving lineages” (FELs)—a subclade within the order Pichiales and the Wickerhamiella/Starmerella (W/S) clade (order Dipodascales)—are described here for the first time, while the third corresponds to a previously documented Hanseniaspora FEL. Examination of genome stability gene repertoires revealed a set of genes predominantly absent in these three FELs, suggesting a potential role in the observed acceleration of evolutionary rates. In the W/S clade, genomic signatures are consistent with a substantial mutational burden, including pronounced A|T bias and endogenous DNA damage. Interestingly, we found that the W/S clade also contains DNA repair genes possibly acquired through horizontal gene transfer, including a photolyase of bacterial origin. These findings highlight how hypermutators can persist across macroevolutionary timescales, potentially linked to the loss of genes related with genome stability, with horizontal gene transfer as a possible avenue for partial functional compensation.

DNA repair↗
DOE OSTI2021

Preliminary Environmental and Financial Viability Analysis of Circular Economy Scenarios for Satisfying PV System Service Lifetime

PV deployment has grown rapidly in recent decades, and this growth is expected to continue. At the same time, the rapid increase in PV panel efficiencies offers the opportunity to repower/revamp existing installations - replacing operational, lower-efficiency panels before the end of their 30-year service lifetime with newer, higher-efficiency panels. As a result, an increasing volume of PV panels could be decommissioned well before reaching the end of their 30-year service lifetime. Two broad strategies can be applied to manage the expected increase in decommissioned PV panels: (i) recycle prematurely decommissioned panels, and (ii) prevent recycling of these panels by satisfying the typical service lifetime of 30 years through circular economy strategies such as repair and reuse. Each strategy presents an environmental and economic trade-off. Retaining and satisfying the lifetime of the older, lower-efficiency panels avoids environmental burdens from recycling or landfilling but incurs burdens from additional repair and forgoing the opportunity to install newer panels with greater electricity-generation capabilities. This study assesses whether satisfying the expected service lifetime of a PV system through circular economy scenarios generates a greater environmental and financial benefit than recycling used panels and installing newer panels with higher efficiencies. The circular economy scenarios include repair and reuse of the PV system. Specifically, the study determines whether it is better for the environment to keep a PV panel in use for its 30-year service life after accounting for potential repair and additional transportation, or to replace older panels with more efficient new ones. In addition, we explore whether satisfying the service lifetime of PV panels proves competitive with the recycling route from a financial perspective.

14 SOLAR ENERGY↗
DOE OSTI2025

Meshfree simulation and prediction of recrystallized grain size in friction stir processed 316L stainless steel

Friction stir processing (FSP) is a promising solid-phase microstructural modification technique that can repair and enhance damaged stainless steel surfaces exposed to harsh environments. The quality of the repaired material is closely correlated to the recrystallized grain size in the stir zone (SZ), which is influenced by the thermomechanical conditions dictated by FSP process parameters. Thus, establishing a reliable relationship between these parameters and recrystallized grain size in the SZ is crucial for optimizing repair quality. However, existing experimental approaches often rely on indirect temperatures measured far from the SZ, along with rough strain rate estimations, which are imprecise and time-consuming. Meanwhile, existing mesh-based modeling methods usually face numerical challenges when dealing with the large material deformations inherent in FSP. Here, to address these issues, this study introduces a meshfree process model for FSP based on the smoothed particle hydrodynamics (SPH) method, aimed at predicting process conditions under different parameters. The model is validated using experimental data from 11 combinations of tool traverse and rotation speeds on 316 L stainless steel. Correlations between process parameters, material flow, temperature, strain, strain rate, and recrystallized grain size are revealed through SPH simulations and electron backscatter diffraction (EBSD) imaging. The results show that in situ SZ temperatures range from 1071 to 1322°C, which exceed the tool temperature by over 300°C. Furthermore, SZ temperature, strain rate, and grain size increase monotonically with higher tool temperature and faster traverse speed. A relationship is then established between the model-predicted Zener-Hollomon parameter and the recrystallized grain size based on EBSD data, expressed as ln(d) = -0.364 ln(Z) + 14.673. Finally, this relationship exhibits satisfactory accuracy with errors of less than 26.9% in predicting grain sizes at various SZ locations, which offers valuable insights for optimizing FSP repair processes for 316 L stainless steel.

316L stainless steel↗
DOE OSTI2021

Switching Device-Cognizant Sequential Distribution System Restoration

This paper presents an optimization framework for sequential reconfiguration using an assortment of switching devices and repair process in distribution system restoration. Compared to existing studies, this paper considers types, capabilities and operational limits of different switching devices, making it applicable in practice. We develop a novel multi-phase method to find the optimal sequential operation of various switching devices and repair faulted areas. We consider circuit breakers, reclosers, sectionalizers, load breaker switches, and fuses. The switching operation problem is decomposed into two mixed-integer linear programming (MILP) subproblems. The first subproblem determines the optimal network topology and estimates the number of steps to reach that topology, while the second subproblem generates a sequence of switching operations to coordinate the switches. For repairing the faults, we design an MILP model that dispatches repair crews to clear faults and replace melted fuses. After clearing a fault, we update the topology of the network by generating a new sequence of switching operations, and the process continues until all faults are cleared. To improve the computational efficiency, a network reduction algorithm is developed to group line sections, such that only switchable sections are present in the reduced network. The proposed method is validated on the IEEE 123-bus and 8500-bus systems.

distribution system↗
DOE OSTI2025

Plant metacaspases orchestrate wound‐induced pathways for immunity and tissue regeneration

Wounding in plants elicits immunity and tissue repair, but how these responses are coordinated has yet to be elucidated. While plant metacaspases resemble animal caspases in structure and immunity induction, their role in tissue repair and regeneration is unknown. Using Arabidopsis mutants lacking type II metacaspases AtMC4 or AtMC9, we found that the majority of the highly induced, wound-responsive genes in Arabidopsis thaliana are suppressed by the loss of AtMC4, while AtMC9 plays an auxiliary role in defense activation. Specifically, AtMC4, but not AtMC9, is required for the activation of genes involved in tissue repair, such as the developmental regulator WOX5, as well as for root regeneration from excised leaves. Instead, AtMC9 mediates the repression of a subset of basal immunity genes, which modifies the wound-activated defense response from that induced by molecular patterns such as the bacterial flg22 elicitor. Our results thus reveal a conserved protease module that coordinates plant defense and tissue repair upon wounding. They could be new targets to improve crop performance and plant transformation protocols that involve tissue wounding before transgenic plant selection and regeneration. The groups of genes with distinctive requirements for the two metacaspases could provide markers to dissect how these specialized proteases affect different response pathways that underpin the multifaceted wounding response.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Fiber-optic sensor packaging assessment and benchmarking for embedded sensing applications

Fiber optic-based sensing for non-destructive evaluation (NDE) and structural health monitoring of various infrastructure and energy assets is an increasingly important sensing scheme. Because of their immunity to electromagnetic interferences, versatility in sensing mechanisms and designs as well as capability for distributed sensing, the fiber optic sensing is of great interest for embedding within infrastructures using advanced manufacturing methods. However, the protection of fiber optic sensors during advanced manufacturing-based embedding is an important aspect for infrastructure monitoring in practice. While successful installation of fiber optic sensors has been accomplished through application of epoxy or adhesives on infrastructure surfaces, there has been only limited investigation of fiber protection packaging schemes which are compatible with in-situ repair techniques such as the metallic cold-spray. With increasing interest and importance of cold spray-based repair processes, the integration of fiber optic sensors simultaneously during the repair is equally important. In this work, we focus our efforts on investigating various types of packaging schemes for their compatibility and integrability on the surfaces of metallic structures such as oil and gas pipelines during an in-situ repair coating. First, we consider sandblasting using silica sand particles of various size for optical fibers on the surface of a metallic coupon as a useful proxy test of sensor packaging stability. Structural damage of packaging is characterized by means of optical microscopy and the optical integrity of embedded fiber optic cables is examined using optical backscatter reflectometry (OBR). In addition, initial investigation of metallic cold-spray embedded fiber optic cables under various packaging on metallic substrates is also considered with early conclusions and future directions.

Fiber-optic sensors, Sensors packaging, Metallic C↗
DOE OSTI2023

Design Considerations and Analysis of Multi-Level Erasure Coding in Large-Scale Data Centers

Multi-level erasure coding (MLEC) has seen large deployments in the field, but there is no in-depth study of design considerations for MLEC at scale. In this paper, we provide comprehensive design considerations and analysis of MLEC at scale. We introduce the design space of MLEC in multiple dimensions, including various code parameter selections, chunk placement schemes, and various repair methods. We quantify their performance and durability, and show which MLEC schemes and repair methods can provide the best tolerance against independent/correlated failures and reduce repair network traffic by orders of magnitude. To achieve this, we use various evaluation strategies including simulation, splitting, dynamic programming, and mathematical modeling. We also compare the performance and durability of MLEC with other EC schemes such as SLEC and LRC and show that MLEC can provide high durability with higher encoding throughput and less repair network traffic over both SLEC and LRC.

Wang, Meng↗
DOE OSTI2023

Characterizing inhibitors of human AP endonuclease 1

AP endonuclease 1 (APE1) processes DNA lesions including apurinic/apyrimidinic sites and 3´-blocking groups, mediating base excision repair and single strand break repair. Much effort has focused on developing specific inhibitors of APE1, which could have important applications in basic research and potentially lead to clinical anticancer agents. We used structural, biophysical, and biochemical methods to characterize several reported inhibitors, including 7-nitroindole-2-carboxylic acid (CRT0044876), given its small size, reported potency, and widespread use for studying APE1. Intriguingly, NMR chemical shift perturbation (CSP) experiments show that CRT0044876 and three similar indole-2-carboxylic acids bind a pocket distal from the APE1 active site. A crystal structure confirms these findings and defines the pose for 5-nitroindole-2-carboxylic acid. However, dynamic light scattering experiments show the indole compounds form colloidal aggregates that could bind (sequester) APE1, causing nonspecific inhibition. Endonuclease assays show the compounds lack significant APE1 inhibition under conditions (detergent) that disrupt aggregation. Thus, binding of the indole-2-carboxylic acids at the remote pocket does not inhibit APE1 repair activity. Myricetin also forms aggregates and lacks APE1 inhibition under aggregate-disrupting conditions. Two other reported compounds (MLS000552981, MLS000419194) inhibit APE1 in vitro with low micromolar IC50 and do not appear to aggregate in this concentration range. However, NMR CSP experiments indicate the compounds do not bind specifically to apo- or Mg 2+ -bound APE1, pointing to a non-specific mode of inhibition, possibly DNA binding. Our results highlight methods for rigorous interrogation of putative APE1 inhibitors and should facilitate future efforts to discover compounds that specifically inhibit this important repair enzyme.

59 BASIC BIOLOGICAL SCIENCES↗