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The Shuttle Program initiated an Extravehicular Activity (EVA) Probabilistic Risk Assessment (PRA) to assess the risks associated with performing a Shuttle Thermal Protection System (TPS) repair during the Space Transportation System (STS)-125 Hubble repair mission as part of risk trades between TPS repair and crew rescue.
Transpiration-cooled fasteners are proposed that operate like an open-loop heat pipe (self-tapping screws, bolts, and spikes) for use in on-orbit repair of thermal- insulation of a space shuttle or other spacecraft. By limiting the temperature rise of such a fastener and of the adjacent repair material and thermal protection system, the transpiration cooling would contribute to the ability of the repair to retain its strength and integrity in the high-heat-flux, oxidizing environment of reentry into the atmosphere of the Earth. A typical fastener according to the proposal would include a hollow refractory-metal, refractory-composite, or ceramic screw or bolt, the central cavity of which would be occupied by a porous refractory- metal or ceramic plug that would act as both a reservoir and a wick for a transpirant liquid. The plug dimensions, the plug material, and the sizes of the pores would be chosen in conjunction with the transpirant liquid so that (1) capillary pumping could be relied upon to transport the liquid to the heated surface, where the liquid would be vaporized, and (2) the amount of liquid would suffice for protecting against the anticipated heat flux and integrated heat load.
Reliability analysis often assumes that a complex system can be kept operating indefinitely with scheduled maintenance and emergency repair using a stock of spare parts, as long as the spare parts are not depleted. This assumption seems justified for well-tested, widely used, long operational systems with a multigenerational history of failure, redesign, and reliability growth. It seems doubtful that newer, relatively untried, high technology space systems can always be repaired. We cannot assume space systems will have a low rate of random failures that can all be repaired with a few identical spares. New untried systems usually have a high initial failure rate, called infant mortality, due to errors in requirements, design, parts, materials, and operations planning. These problems can cause groups of related failures called Common Cause Failures (CCFs). The practical definition of a CCF is any failure mode that cannot be cured using identical redundant systems or spare parts. Systems with CCFs may fail repeatedly for the same reason. Can a life support system be kept operating on the way to Mars using only redundant systems and spare parts? The failure history of International Space Station (ISS) life support systems suggests that CCFs are likely to occur and will probably require design changes rather than being reparable with spare parts.
In recent time, solid state crack repair techniques in spent nuclear fuel dry storage canisters (SNF-DSC) have garnered significant interest. Plates of austenitic stainless steels are usually arc welded to fabricate the cylindrical canisters which are prone to chloride-induced stress corrosion cracking. Friction stir welding (FSW) is considered to be a potential candidate for damage repair. In this work, electrical discharge machining was used to simulate cracks in 304L stainless steel plates of 12.7 mm thickness. Subsequently, isothermal FSW was carried out at two different temperatures (725 and 825°C) in order to repair the simulated crack. Microstructure-mechanical property correlations in FSWed plates were studied in detail. Significant grain refinement observed in the stir zone (SZ) was attributed to dynamic recrystallization occurring during FSW. A comparison of Vickers microhardness showed higher hardness and homogeneity in the 725°C SZ than its 825°C counterpart. The fraction of S3 boundary is found to be low in the SZ as compared to base metal (BM). Yield strength of the joints was found to be approximately 100 MPa higher than that of the BM accompanied by a drop in ductility by a factor of 2. Residual stress profile across 825°C weld was measured using x-ray diffraction.
Y-box binding protein 1 (YB-1) overexpression is associated with chemotherapy- and radiation therapy resistance. Ionizing radiation (IR), receptor tyrosine kinase ligands, and mutation in KRAS gene stimulate activation of YB-1. YB-1 accelerates the repair of IR-induced DNA double-strand breaks (DSBs). Ribosomal S6 kinase (RSK) is the main kinase inducing YB-1 phosphorylation. We investigated the impact of RSK targeting on DSB repair and radiosensitivity.
Here, friction surfacing (FS) was investigated as a method for sealing 50 μm wide thru-cracks in 3-mm-thick 304L stainless steel (304L) plate. Friction surfacing was performed using two sizes of 304L consumable rod, with diameters of 9.52 mm and 12.7 mm, on two substrate conditions (clean and oxidized). Friction surfacing was able to deposit a 600 μm thick coating and repair cracks to a depth of 100 μm - 200 μm below the original surface, when using the 12.7-mm-diameter consumable rod for both substrate conditions. Helium leak rates of 10 -10 atm-cc/s were achieved on crack repairs, designating them as leak-tight by the ANSI N14.5 standard. Optical and scanning electron microscopy were used to investigate the coating microstructure and bond interfaces. In this study, the 12.7-mm-diameter rod performed better with disruption of the oxide layer on the oxidized substrate and providing a more homogenous coating. Mechanical properties of the coated samples were evaluated by performing micro-indentation, tensile, bending, and adhesion testing. Higher hardness in the coatings was observed due to the fine equiaxed grains resulting from dynamic recrystallization. Complete consolidation of plastically deformed material on the substrate and a strong diffusion bond across the interface was observed. This was reflected in tensile and bending properties of the FS coatings being comparable to those of uncoated specimen. No delamination of the FS coating was observed during adhesion testing. The results demonstrate that friction surfacing is a viable option to seal cracks in stainless steels.
Welding repair of irradiated nuclear reactor materials such as austenitic stainless steels used for the reactor internals has been challenging due to irradiation generated helium in the material matrix over an extended period of time. In this study, improved laser welding techniques, including the novel Auxiliary Beam Stress Improved (ABSI) technique that proactively manages the stresses during laser repair welding is investigated to substantially reduce or avoid the occurrence of intergranular helium-induced cracking (HeIC). Here, laser weld cladding, with and without ABSI technique, was applied to deposit weld metal on irradiated stainless steel (Type 304 L) blocks with various helium concentrations up to approximately 20 atomic parts per million (appm). Welded samples were cross-sectioned and analyzed using optical and electron microscopes. It was found that, with the improved laser welding techniques, no macroscopic (millimeter-sized) cracks were observed in any of the samples. Microscopic (less than 50 μm) cracks were present in the heat affected zone. Statistical analysis on the sample with the highest helium concentration (~20 appm) reveals that the ABSI technique could effectively reduce the size and amounts of microscopic cracks.
Welding repair of irradiated nickel-based alloys, such as Alloy 182, poses a significant challenge due to helium-induced cracking (HeIC) and grain boundary degradation (GBD) in the heat affected zone, driven by helium accumulation at grain boundaries and welding-induced tensile stresses. This study investigates the weldability of irradiated Alloy 182 up to 15 wppm doped boron using both conventional laser welding and the Auxiliary Beam Stress Improved (ABSI) laser welding technique. While HeIC was observed at the weld toe of the entry pass in both methods due to the higher effective heat input associated with the initial pass directly on the base metal, no additional cracking occurred elsewhere, even at elevated helium concentrations. Optical and scanning electron microscopy analysis revealed that the ABSI technique, which introduces additional compressive stresses to counteract solidification-induced tensile stresses, significantly reduced GBD formation, lowering its total count from 1,230 to 339 and decreasing both average and maximum GBD lengths. In conclusion, these results demonstrate that the ABSI technique is a promising approach to mitigate helium-induced damage and improve the weldability of irradiated Alloy 182, offering a viable solution for structural repairs for long-term operation of existing nuclear reactors.
Two technologies, friction surfacing (FS) and cold spray deposition (CSD), have been investigated for field repair of cracks in 304L austenitic stainless steel. Both technologies are low-heat-input, solid-state technologies that do not introduce the detrimental effects of solidification, such as compositionally segregated microstructures and shrinkage stresses. Friction surfacing was performed using a 304L stainless steel rod over the substrate of the same material. Further, the process was performed at a high spindle speed of 20,000 RPM allowing for process forces below 500N to be used effectively. Spherical gas-atomized 304L stainless steel powder, in size range of 25–44 µm, was used as feedstock powder for the cold spray process for deposition on 304L substrates. Both technologies showed leak-tight crack repair capabilities on ~30–50 µm wide simulated through-crack specimens based on helium leak tests.
DNA damage is a constant stressor to the cell. Persistent damage to the DNA over time results in an increased risk of mutation and an accumulation of mutations with age. Loss of efficient DNA damage repair can lead to accelerated ageing phenotypes or an increased cancer risk, and the trade-off between cancer susceptibility and longevity is often driven by the cell's response to DNA damage. High levels of mutations in DNA repair mutants often leads to excessive cell death and stem cell exhaustion which may promote premature ageing. Stem cells themselves have distinct characteristics that enable them to retain low mutation rates. However, when mutations do arise, stem cell clonal expansion can also contribute to age-related tissue dysfunction as well as heightened cancer risk. In this review, we will highlight increasing DNA damage and mutation accumulation as hallmarks common to both ageing and cancer. We will propose that anti-ageing interventions might be cancer preventative and discuss the mechanisms through which they may act.
Second messenger (p)ppGpp (collectively guanosine tetraphosphate and guanosine pentaphosphate) mediates bacterial adaptation to nutritional stress by modulating transcription initiation. More recently, ppGpp has been implicated in coupling transcription and DNA repair; however, the mechanism of ppGpp engagement remained elusive. Here we present structural, biochemical and genetic evidence that ppGpp controls Escherichia coli RNA polymerase (RNAP) during elongation via a specific site that is nonfunctional during initiation. Structure-guided mutagenesis renders the elongation (but not initiation) complex unresponsive to ppGpp and increases bacterial sensitivity to genotoxic agents and ultraviolet radiation. Thus, ppGpp binds RNAP at sites with distinct functions in initiation and elongation, with the latter being important for promoting DNA repair. Our data provide insights on the molecular mechanism of ppGpp-mediated adaptation during stress, and further highlight the intricate relationships between genome stability, stress responses and transcription.
This paper proposes a distribution system restoration model which is in response to multiple outages caused by natural disasters. The proposed restoration model includes the coordination of routing repair crews (RRCs), mobile batterycarried vehicles (MBCVs), and networked microgrids (NMGs) formed by soft open points (SOPs). The travel and repair time constraints are modeled for each RRC; travel path and charging strategy are modeled for each MBCV; and the network reconfiguration is developed considering the optimal operation of SOP-based NMGs. Furthermore, the proposed model is presented as a mixedinteger linear program which is solved by an auxiliary induce function based algorithm to reduce the computational complexity. The modified IEEE 33-bus and 69-bus distribution systems are tested with multiple outages. The presented results demonstrate the effectiveness of the proposed model
Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).
Oxygenic photosynthetic organisms use Photosystem II (PSII) to oxidize water and reduce plastoquinone. Here, we review the mechanisms by which PSII is assembled and turned over in the model green alga Chlamydomonas reinhardtii. This species has been used to make key discoveries in PSII research due to its metabolic flexibility and amenability to genetic approaches. PSII subunits originate from both nuclear and chloroplastic gene products in Chlamydomonas. Nuclear-encoded PSII subunits are transported into the chloroplast and chloroplast-encoded PSII subunits are translated by a coordinated mechanism. Active PSII dimers are built from discrete reaction center complexes in a process facilitated by assembly factors. The phosphorylation of core subunits affects supercomplex formation and localization within the thylakoid network. Proteolysis primarily targets the D1 subunit, which when replaced, allows PSII to be reactivated and completes a repair cycle. While PSII has been extensively studied using Chlamydomonas as a model species, important questions remain about its assembly and repair which are presented here.
The human Rad51 protein is essential for DNA repair by homologous recombination. In addition to Rad51 protein, five paralogs have been identified: Rad51B/Rad51L1, Rad51C/Rad51L2, Rad51D/Rad51L3, XRCC2, and XRCC3. To further characterize a subset of these proteins, recombinant Rad51, Rad51B-(His)(6), and Rad51C proteins were individually expressed employing the baculovirus system, and each was purified from Sf9 insect cells. Evidence from nickel-nitrilotriacetic acid pull-down experiments demonstrates a highly stable Rad51B.Rad51C heterodimer, which interacts weakly with Rad51. Rad51B and Rad51C proteins were found to bind single- and double-stranded DNA and to preferentially bind 3'-end-tailed double-stranded DNA. The ability to bind DNA was elevated with mixed Rad51 and Rad51C, as well as with mixed Rad51B and Rad51C, compared with that of the individual protein. In addition, both Rad51B and Rad51C exhibit DNA-stimulated ATPase activity. Rad51C displays an ATP-independent apparent DNA strand exchange activity, whereas Rad51B shows no such activity; this apparent strand exchange ability results actually from a duplex DNA destabilization capability of Rad51C. By analogy to the yeast Rad55 and Rad57, our results suggest that Rad51B and Rad51C function through interactions with the human Rad51 recombinase and play a crucial role in the homologous recombinational repair pathway.
It has recently been demonstrated experimentally that DNA damage induced by high LET radiation in mammalian cells is non-randomly distributed along the DNA molecule in the form of clusters of various sizes. The sizes of such clusters range from a few base-pairs to at least 200 kilobase-pairs. The high biological efficiency of high LET radiation for induction of relevant biological endpoints is probably a consequence of this clustering, although the exact mechanisms by which the clustering affects the biological outcome is not known. We discuss here results for induction and repair of base damage, single-strand breaks and double-strand breaks for low and high LET radiations. These results are discussed in the context of clustering. Of particular interest is to determine how clustering at different scales affects overall rejoining and fidelity of rejoining of DNA double-strand breaks. However, existing methods for measuring repair of DNA strand breaks are unable to resolve breaks that are close together in a cluster. This causes problems in interpretation of current results from high LET radiation and will require new methods to be developed.
This DAA is for the Phase II webinar presentation of the ARMD-funded SMASH technology. A self-repairing aluminum-based composite system has been developed using liquid-assisted healing theory in conjunction with the shape memory effect of wire reinforcements. The metal matrix composite was thermodynamically designed to have a matrix with a relatively even dispersion of low-melting phase, allowing for repair of cracks at a pre-determined temperature. Shape memory alloy wire reinforcements were used within the composite to provide crack closure. Investigators focused the research on fatigue cracks propagating through the matrix in order to optimize and computer model the SMASH technology for aeronautical applications.
This presentation discusses the development and results of composite patch repair perfromed at Kennedy Space Center. This includes impact damage, patch repair methods, nondestructive evaluation, and edgewise compression testing.