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At least 865 records · Page 48

Novel interaction interfaces mediate the interaction between the NEIL1 DNA glycosylase and mitochondrial transcription factor A

The maintenance of human mitochondrial DNA (mtDNA) is critical for proper cellular function as damage to mtDNA, if left unrepaired, can lead to a diverse array of pathologies. Of the pathways identified to participate in DNA repair within the mitochondria, base excision repair (BER) is the most extensively studied. Protein-protein interactions drive the step-by-step coordination required for the successful completion of this pathway and are important for crosstalk with other mitochondrial factors involved in genome maintenance. Human NEIL1 is one of seven DNA glycosylases that initiates BER in both the nuclear and mitochondrial compartments. In the current work, we scrutinized the interaction between NEIL1 and mitochondrial transcription factor A (TFAM), a protein that is essential for various aspects of mtDNA metabolism. We note, for the first time, that both the N- and C- terminal domains of NEIL1 interact with TFAM revealing a unique NEIL1 protein-binding interface. The interaction between the two proteins, as observed biochemically, appears to be transient and is most apparent at concentrations of low salt. The presence of DNA (or RNA) also positively influences the interaction between the two proteins, and molar mass estimates indicate that duplex DNA is required for complex formation at higher salt concentrations. Hydrogen deuterium exchange mass spectrometry data reveal that both proteins exchange less deuterium upon DNA binding, indicative of an interaction, and the addition of NEIL1 to the TFAM-DNA complex alters the interaction landscape. The transcriptional activity of TFAM appears to be independent of NEIL1 expression under normal cellular conditions, however, in the presence of DNA damage, we observe a significant reduction in the mRNA expression of TFAM-transcribed mitochondrial genes in the absence of NEIL1. Overall, our data indicate that the interaction between NEIL1 and TFAM can be modulated by local environment such as salt concentrations, protein availability, the presence of nucleic acids, as well as the presence of DNA damage.

59 BASIC BIOLOGICAL SCIENCES↗

Erosion, Corrosion and Foreign Object Damage Effects in Gas Turbines [Les consequences de l'endommagement des turbines I gaz par erosion, corrosion et objets étrangers]

The Conference Proceedings contains 31 papers presented at the Propulsion and Energetics Panel Symposium on Erosion, Corrosion and Foreign Object Damage Effects in Gas Turbines which was held from 25-28th April 1994, in Rotterdam, The Netherlands. The Technical Evaluation Report and the Keynote Address are included at the beginning and discussions follow most papers. The Symposium was arranged in the following Sessions: Operational Experience and Requirements (7); Deposition and Erosion (7); Foreign Object Damage (5); Coatings, Repairs and Materials Aspects - 1 (4); Coatings, Repairs and Materials Aspects - 2 (7); and Testing and Certification Procedures (1).

Deposition↗

Radiation-induced chromosome aberrations in ataxia telangiectasia cells: high frequency of deletions and misrejoining detected by fluorescence in situ hybridization

The mechanisms underlying the hyper-radiosensitivity of AT cells were investigated by analyzing chromosome aberrations in the G(2) and M phases of the cell cycle using a combination of chemically induced premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with chromosome painting probes. Confluent cultures of normal fibroblast cells (AG1522) and fibroblast cells derived from an individual with AT (GM02052) were exposed to gamma rays and allowed to repair at 37 degrees C for 24 h. At doses that resulted in 10% survival, GM02052 cells were approximately five times more sensitive to gamma rays than AG1522 cells. For a given dose, GM02052 cells contained a much higher frequency of deletions and misrejoining than AG1522 cells. For both cell types, a good correlation was found between the percentage of aberrant cells and cell survival. The average number of color junctions, which represent the frequency of chromosome misrejoining, was also found to correlate well with survival. However, in a similar surviving population of GM02052 and AG1522 cells, induced by 1 Gy and 6 Gy, respectively, AG1522 cells contained four times more color junctions and half as many deletions as GM02052 cells. These results indicate that both repair deficiency and misrepair may be involved in the hyper-radiosensitivity of AT cells.

NASA Center JSC↗

Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations

PURPOSE: To investigate the role of kinetics in the processing of DNA double strand breaks (DSB), and the formation of simple chromosome exchange aberrations following X-ray exposures to mammalian cells based on an enzymatic approach. METHODS: Using computer simulations based on a biochemical approach, rate-equations that describe the processing of DSB through the formation of a DNA-enzyme complex were formulated. A second model that allows for competition between two processing pathways was also formulated. The formation of simple exchange aberrations was modelled as misrepair during the recombination of single DSB with undamaged DNA. Non-linear coupled differential equations corresponding to biochemical pathways were solved numerically by fitting to experimental data. RESULTS: When mediated by a DSB repair enzyme complex, the processing of single DSB showed a complex behaviour that gives the appearance of fast and slow components of rejoining. This is due to the time-delay caused by the action time of enzymes in biomolecular reactions. It is shown that the kinetic- and dose-responses of simple chromosome exchange aberrations are well described by a recombination model of DSB interacting with undamaged DNA when aberration formation increases with linear dose-dependence. Competition between two or more recombination processes is shown to lead to the formation of simple exchange aberrations with a dose-dependence similar to that of a linear quadratic model. CONCLUSIONS: Using a minimal number of assumptions, the kinetics and dose response observed experimentally for DSB rejoining and the formation of simple chromosome exchange aberrations are shown to be consistent with kinetic models based on enzymatic reaction approaches. A non-linear dose response for simple exchange aberrations is possible in a model of recombination of DNA containing a DSB with undamaged DNA when two or more pathways compete for DSB repair.

DNA Damage↗

Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together?

Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that are deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale, yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired. The cause and natural function of such breaks remains a mystery; however, their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes. If this is true, the target gene(s) of recombination and their significance remain to be determined.

NASA Discipline Cell Biology↗

DNA Damage Response to Low and High-LET in a Large Cohort of Mice and Humans and Latest Advancement in NASA Space Omics

This presentation will first focus on a thorough evaluation of the DNA damage response to both low and high-LET in a cohort of 76 mice primary skin fibroblast derived from 15 different strains or in human blood mononuclear cells derived from 550 healthy donors. In both the human and mice work, we have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Results on humans are still preliminary as we are still in the process of collecting and isolating primary blood mononuclear cells from 500 to 800 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. The second part of the talk will focus on describing GeneLab: The NASA Systems Biology Platform for Space Omics Repository, Analysis and Visualization. NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). Started as a repository designed to archive precious omics from space experiments, GeneLab has expanded its scope to maximize the intelligibility of the raw data (e.g. RNAseq, microarray, WGBS, metagenome), particularly for users with limited bioinformatics knowledge. As such GeneLab is now providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome), to help users explore important questions: Which genes or proteins are expressed differently in space for various living organisms? What are the consequences arising from these changes? What specifics DNA mutations or epigenetic changes happen in space? What species or genetic features lead to better adaption to such a unique environment? In this presentation, we will report on the current and future objectives for GeneLab, and review recent published studies relating molecular changes observed in various animal models and tissue with microgravity, radiation, circadian rhythm, hydration and carbon dioxide conditions.

DNA repair kinetics↗

Carbon Fiber Reinforced Epoxy Vitrimer: Robust Mechanical Performance and Facile Hydrothermal Decomposition in Pure Water

Conventional carbon fiber reinforced thermosetting polymers (CFRPs) are neither recyclable nor repairable due to their crosslinked network. The rapid growing CFRP market raises a serious concern of the waste management. In this work, a viable method to develop a readily recyclable CFRP based on epoxy vitrimer is introduced. First, a self-catalytic epoxy prepolymer with built-in hydroxy and tertiary amine groups is designed, which upon reaction with an anhydride formed a catalyst-free epoxy vitrimer. The epoxy prepolymer is synthesized from a diamine and an excess of bisphenol A epoxy resin. The hydroxyls and tertiary amines of the epoxy prepolymer efficiently catalyze both curing and the dynamic transesterification of the crosslinked polymer without the need of a catalyst. Then, the epoxy vitrimer is used as the matrix resin to prepare CFRP. The resulting CFRP exhibited a tensile strength as high as 356 MPa. More interestingly, the matrix of the CFRP is efficiently degraded in pure water at above 160 °C. This is because the built-in tertiary amines catalyze the hydrolysis of the ester bonds of the crosslinked network. The simple method developed in this work provides a framework for the development of recyclable CFRP.

Liu, Tuan↗

PV Field Reliability Status--Analysis of 100,000 Solar Systems

In this paper, we analyzed annual production data from 100 000 photovoltaic systems as well as comments relating to their performance and maintenance. Our analysis revealed that 80% to 90% of all systems performed within 10% of the predicted production or better. Also, 56% of the systems were still performing above P50 or the median at 5 years. However, a small but significant tail of about 7000 systems perform below P90 expectations. In general, residential systems have a lower rate of failure than utility or commercial systems. Despite higher rates of component failures, utility systems lose less power than residential or commercial systems. This outcome is likely due to closer monitoring and better operations and maintenance practices. Inverters are still the components that reportedly fail most often (4%-6%), but other failures such as unspecified repair and meters cause more production loss. Reported module failures are relatively rare (0.2%) and are within the range of historical values. Installation quality affects performance and safety as indicated by data showing connector, wiring, breaker, and fuse failures due to undersizing, electrical design, and improper connection. Lastly, early detection of degradation and proactive response resulted in less impact on production than reactive, unplanned repairs.

14 SOLAR ENERGY↗

Techno‐Economic Analysis of Additively‐Manufactured Wind Turbine Blade Tips That Enable Technology Integration

The Additively‐Manufactured, System‐Integrated Tip (AMSIT) project is leveraging the flexibility of 3D printing to integrate several technologies in a wind turbine blade tip, while reducing the levelized cost of electricity (LCOE) produced. The design integration is demonstrated for a 200‐kW–scale turbine with 13‐m blades, with the outer 15% of the blade replaced with a 3D‐printed design. Aerodynamic performance is enhanced without increasing swept area through inclusion of a winglet and surface texturing, both challenging for traditional manufacturing. Longevity and durability are improved through integrated lightning and leading edge erosion protection. Increased power, reduced repair frequency, and ease of repair through blade modularity all contribute to reduced LCOE. The analysis is also extended to modern MW‐scale designs to estimate the impact of the technology at scale, demonstrating the potential to reduce LCOE significantly for modern onshore turbines, with even higher potential savings offshore.

3D printing↗

Optimizing power system restoration with damaged communications

Utility procedures for power system blackstart and restoration typically assume that energization decisions can be reliably communicated across the grid. In reality, the communications and control network would likely also be affected in power outages, such as those caused by extreme weather events or cyber-attacks. This paper studies the effect of damage to the power system communications and control infrastructure on restoration operations following a blackout. We model the communications infrastructure as a graph, overlaying the power grid, and imposing the requirement that every energized element in the power grid be observable from a control center. We expand on a specialized branch-and-bound algorithm from the literature to optimize the restoration process and devise an initialization heuristic and a rounding heuristic to improve solution speed. We perform numerical experiments on synthetic systems for Illinois and Texas with outages based on a solar flare or hurricane. We compare the results of our specialized branch-and-bound algorithm to the results from (i) the initialization heuristic alone, (ii) a variation of this heuristic that we use as a baseline, and (iii) the restoration optimization for the power system without communications constraints. Here, we find that damage to the communications infrastructure significantly increases the time required to re-energize the grid. Moreover, by simultaneously optimizing communications repairs and grid energization decisions, we are able to re-energize the grid significantly faster than if communications repairs and energization decisions were made independently or with partial coordination, motivating improvements to current industry practice.

97 MATHEMATICS AND COMPUTING↗

In-situ qualification and physics-based process design for aerosol jet printing via spatially correlated light scattering measurements

Aerosol jet printing is a contactless, digital, and additive technique broadly used for manufacturing flexible, hybrid, and conformal electronics. However, batch-to-batch variability has hindered widespread industry adoption and scaling to production volumes. Recently, light scattering measurements have emerged as a tool to measure aerosol volume fraction – a key parameter determining deposition rate – and have proven an effective feedback source for closed loop control on timescales ranging from minutes to hours. Here, the efficacy of light scattering measurements as a tool for in-situ qualification over shorter time durations is explored. To be the linear relationship between light scattering measurements and deposition rate was validated at 500 ms time intervals, allowing deposition rate to be mapped to positional coordinates and providing a new data stream to drive quality control assessments. Because light scattering measurements are indicative of a physical process parameter, they were substituted into equations for resistance and sheet resistance, resulting in predictions nominally within 10% of measured values for sets of printed devices. Finally, to highlight a more active utility, light scattering measurements were employed in a print repair framework, successfully repairing prints with randomly induced defects to within 5% of the measured resistance of a control set.

36 MATERIALS SCIENCE↗

Cold spray technology in nuclear energy applications: A review of recent advances

Cold spray technology is a promising solid-state, powder-based deposition methods for fabrication of coatings, near-net-shape manufacturing, and component repair. In recent years, this technology has been investigated for many applications in the nuclear energy sector. For example, it has been explored for the deposition of coatings of corrosion and oxidation materials on zirconium-alloys fuel claddings in light water reactors (LWR) for achieving more accident-tolerant fuel (ATF) cladding. Other examples of its use for nuclear energy applications include coatings for enhancements in wear resistance and heat transfer, near-net shape manufacturing of next-generation fuel claddings of oxide dispersion-strengthened (ODS) steels, and for mitigation and repair of potential chloride induced stress corrosion cracking in used fuel storage canister systems. This work reviews published literature on the application of cold spray process for nuclear energy applications, while pointing to gaps that have yet to be addressed.

36 MATERIALS SCIENCE↗

Site-specific surface reactivity on MgO for atomic layer deposition via selective hydration

Atomic layer deposition (ALD) is a powerful technique for thin film synthesis, offering atomic-scale precision and conformality. While ALD of MgO has been widely studied for applications in energy storage and microelectronics, its potential as surface on which deposition may be selective and defects repaired remains underexplored. Here, we present a combined theoretical and experimental investigation of MgO surface hydration and its implications for targeted ALD growth using water and dimethyl aluminum isopropoxide (DMAI) as reactants. We perform density functional theory (DFT) calculations to examine molecular and dissociative H 2 O adsorption on MgO (100) terraces and step-edge sites, including pristine surfaces and those with Mg/O vacancies. Reaction Gibbs free energies are calculated under various conditions to quantify surface reactivity. Our findings reveal facet- and defect-dependent hydration behaviors that align with experimental ALD growth trends on MgO (100). This study provides a molecular-level understanding of MgO surface chemistry critical for optimizing ALD processes for thin film growth and defect repair.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Room temperature slot-die coated perovskite layer modified with sulfonyl-γ-AApeptide for high performance perovskite solar devices

Perovskite solar cells (PSCs) exhibited remarkable progress for small aperture area cells, however, the performance of its counterpart, large aperture area cells, lags due to non-uniform and defective perovskite layers. Here, we fabricate reproducible large area homogeneous perovskite films at room temperature and without controlling humidity (up to 40 % RH) with a slot die coater on a c-TiO 2 layer deposited using a large area chemical bath. A new artificial peptide – sulfonyl-γ-AApeptide (F-GLU-S) was employed to modify the slot-die coated perovskite surface, grain boundaries and electronic defects. The multi-functional F-GLU-S with carbonyl, carboxyl, sulfonyl, benzene, and chloro groups was capable of strongly interacting with the perovskite layer and repairing the uncoordinated Pb 2+ ions and halide vacancies. As a result, both the electron and hole densities of defects were significantly suppressed; consequently, the non-radiative recombination was effectively suppressed for the modified device which can be explicitly seen in the device performance where both V oc and FF of the modified device improved considerably. Therefore, F-GLU-S modified slot-die coated MAPbI 3 – based devices demonstrated outstanding performance of 21.44 % PCE with a V oc of 1.13 V, J sc of 24.64 cm –2 , and FF 76.99 %. Furthermore, F-GLU-S passivation impeded the infiltration of moisture and oxygen due to its hydrophobic nature and defect repair potential. As a result, the modified device retained above 92 % of its original PCE after 720 h in air (room temperature and 40–60 % RH).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Intrinsic self-stressing and low carbon Engineered Cementitious Composites (ECC) for improved sustainability

Highlights: • A self-stressing criterion for ECC was established and experimentally verified. • An intrinsic self-stressing ECC was developed by utilizing LC3 and CSA cement. • Initial maximum expansion and later expansion loss were successfully tailored. • Expansion mechanism was identified by XRD patterns. • Self-stressing ECC has 64% of the carbon footprint of conventional concrete. Engineered Cementitious Composites (ECC) is an emerging cementitious composite material with ultra-high ductility. However, its higher cement dosage limits its material greenness and leads to concerns with drying shrinkage. In this research, an ECC utilizing limestone calcined clay cement (LC3) and calcium sulphoaluminate cement (CSA) is investigated, focusing on minimizing the material's embodied carbon while enhancing its durability with intrinsic self-stressing functionality. A self-stressing criterion is theoretically established and experimentally verified. X-ray diffraction patterns reveal an ettringite quantity that modulates the initial expansion and later expansion-reversal of LC3-CSA-ECC to support a persistent self-stressing mechanism. LC3-CSA-ECC has a lower (64%) carbon footprint and similar embodied energy compared to conventional concrete. When combined with the durability advantage (tiny crack, high ductility of 5.5%, and self-stressing function), this low carbon self-stressing ECC holds promise as a sustainable repair material that lowers the embodied and operational carbon in civil infrastructure.

36 MATERIALS SCIENCE↗

The crystal structure of Vibrio cholerae (6-4) photolyase reveals interactions with cofactors and a DNA-binding region

Photolyases (PLs) reverse UV-induced DNA damage using blue light as an energy source. Of these PLs, (6-4) PLs repair (6-4)-lesioned photoproducts. We recently identified a gene from Vibrio cholerae (Vc) encoding a (6-4) PL, but structural characterization is needed to elucidate specific interactions with the chromophore cofactors. Here, we determined the crystal structure of Vc (6-4) PL at 2.5 Å resolution. Our high-resolution structure revealed that the two well-known cofactors, flavin adenine dinucleotide and the photoantenna 6,7-dimethyl 8-ribityl-lumazin (DMRL), stably interact with an α-helical and an α/β domain, respectively. Additionally, the structure has a third cofactor with distinct electron clouds corresponding to a [4Fe-4S] cluster. Moreover, we identified that Asp106 makes a hydrogen bond with water and DMRL, which indicates further stabilization of the photoantenna DMRL within Vc (6-4) PL. Further analysis of the Vc (6-4) PL structure revealed a possible region responsible for DNA binding. The region located between residues 478 to 484 may bind the lesioned DNA, with Arg483 potentially forming a salt bridge with DNA to stabilize further the interaction of Vc (6-4) PL with its substrate. Our comparative analysis revealed that the DNA lesion could not bind to the Vc (6-4) PL in a similar fashion to the Drosophila melanogaster (Dm, (6-4)) PL without a significant conformational change of the protein. The 23rd helix of the bacterial (6-4) PLs seems to have remarkable plasticity, and conformational changes facilitate DNA binding. In conclusion, our structure provides further insight into DNA repair by a (6-4) PL containing three cofactors.

(6-4) lesioned photoproduct↗

Investigation of interfacial structures for hybrid manufacturing

Hybrid manufacturing is a combination of additive and subtractive manufacturing in a single machine. Typically, planar substrate substrates are used for deposition and do not correspond to scenarios encountered in repair applications where the substrate can often be non-planar. Hybrid manufacturing opens the possibility for repairs by leveraging the five-axis mill to prepare the substrate for deposition. However, as the substrate geometry changes, so does the associated heat transfer during deposition and subsequent microstructures. This paper focuses on understanding the changes in microstructure and material properties with changing substrate geometries.

36 MATERIALS SCIENCE↗

Reinforcing the exit hole from friction stir welding and processing

After friction stir welding/processing (FSW/P), an exit hole remains at the end of the run, which can be the weakest region of the welded/processed workpiece. In addition, tensile residual stress around the exit hole resulting from heating during FSW/P facilitates incipient crack initiating from the exit hole under external loading. Current solutions include removing or repairing the exit hole, which are time-consuming and costly. Here, we propose a novel method to reinforce the exit hole by applying an additional FSW/P pass around it, in a way that replaces preexisting tensile residual stress with compressive residual stress. Under external loading, there is no evident strain accumulation around the exit hole, and the workpiece ultimately fails along the FSW/P heat affected zone. This method provides a more convenient way to reinforce the exit hole than the current exit-hole repair or removal methods for industrial applications.

36 MATERIALS SCIENCE↗