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At least 127 records · Page 7

Reliability and Maintainability Data for Liquid Metal Cooling Systems

One of the coolants of interest for future fusion breeding blankets is lead-lithium. As a liquid metal it offers the advantages of high temperature operation for good station efficiency, low pressure, and moderate flow rate. This coolant is also under examination for use in test blanket modules to be used in the ITER international project. To perform reliability, availability, maintainability and inspectability (RAMI) assessment as well as probabilistic safety assessment (PSA) of lead-lithium cooling systems, component failure rate data are needed to quantify the system models. RAMI assessment also requires repair time data and inspection time data. This paper presents a new survey of the data sets that are available at present to support RAMI and PSA quantification. Recommendations are given for the best data values to use when quantifying system models.

maintainability data↗

Reliability and Maintainability Data for Lead Lithium Cooling Systems

This article presents component failure rate data for use in assessment of lead lithium cooling systems. Best estimate data applicable to this liquid metal coolant is presented. Repair times for similar components are also referenced in this work. These data support probabilistic safety assessment and reliability, availability, maintainability and inspectability analyses.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Mechanical Properties of Irradiated Polarization-Maintaining Optical Fibers

Polarization-maintaining optical fibers, referred to as PANDA fibers, were subjected to Cobalt 60 radiation (300,000 Rad). The mechanical properties of the PANDA fibers were measured after exposure to gamma radiation and compared to non-irradiated PANDA fibers.

optical fibers irradiated fibers PANDA fibers pola↗

NASA Exploration Systems Maintainability Standards for Artemis and Beyond

This assessment was requested by the NASA Engineering and Safety Center (NESC), which, based on findings from the NESC study “Safe Human Expeditions Beyond Low Earth Orbit (LEO)” (Valinia et al., 2022), determined its topic to be an underrecognized critical and urgent Agency need, due to impending Artemis vehicle procurements. The principal objective of this assessment was to review and update current Agency-level maintainability requirements for space systems to support crew on expeditions beyond LEO in both preventive and corrective maintenance. This report contains the results of the NESC assessment.

Orbital Replacement Units↗

Maintainability and Supportability

NASA policy addresses the need for agency-funded programs and projects that develop or procure reusable or maintainable flight hardware or programmatic / mission-specific ground hardware to define and implement measures that provide life-cycle support to increase the probability of mission success and to control and reduce life-cycle costs and risks.

Maintainability↗

Lignocellulose solubilization and conversion by extremely thermophilic Caldicellulosiruptor bescii improves by maintaining metabolic activity

Abstract The extreme thermophile Caldicellulosiruptor bescii solubilizes and metabolizes the carbohydrate content of lignocellulose, a process that ultimately ceases because of biomass recalcitrance, accumulation of fermentation products, inhibition by lignin moieties, and reduction of metabolic activity. Deconstruction of low loadings of lignocellulose (5 g/L), either natural or transgenic, whether unpretreated or subjected to hydrothermal processing, by C. bescii typically results in less than 40% carbohydrate solubilization. Mild alkali pretreatment (up to 0.09 g NaOH/g biomass) improved switchgrass carbohydrate solubilization by C. bescii to over 70% compared to less than 30% for no pretreatment, with two‐thirds of the carbohydrate content in the treated switchgrass converted to acetate and lactate. C. bescii grown on high loadings of unpretreated switchgrass (50 g/L) retained in a pH‐controlled bioreactor slowly purged (τ = 80 hr) with growth media without a carbon source improved carbohydrate solubilization to over 40% compared to batch culture at 29%. But more significant was the doubling of solubilized carbohydrate conversion to fermentation products, which increased from 40% in batch to over 80% in the purged system, an improvement attributed to maintaining the bioreactor culture in a metabolically active state. This strategy should be considered for optimizing solubilization and conversion of lignocellulose by C. bescii and other lignocellulolytic microorganisms.

Straub, Christopher T.↗

Maintaining Trust in Reduction: Preserving the Accuracy of Quantities of Interest for Lossy Compression

As the growth of data sizes continues to outpace computational resources, there is a pressing need for data reduction techniques that can significantly reduce the amount of data and quantify the error incurred in compression. Compressing scientific data presents many challenges for reduction techniques since it is often on non-uniform or unstructured meshes, is from a high-dimensional space, and has many Quantities of Interests (QoIs) that need to be preserved. To illustrate these challenges, we focus on data from a large scale fusion code, XGC. XGC uses a Particle-In-Cell (PIC) technique which generates hundreds of PetaBytes (PBs) of data a day, from thousands of timesteps. XGC uses an unstructured mesh, and needs to compute many QoIs from the raw data, f.One critical aspect of the reduction is that we need to ensure that QoIs derived from the data (density, temperature, flux surface averaged momentums, etc.) maintain a relative high accuracy. We show that by compressing XGC data on the high-dimensional, nonuniform grid on which the data is defined, and adaptively quantizing the decomposed coefficients based on the characteristics of the QoIs, the compression ratios at various error tolerances obtained using a multilevel compressor (MGARD) increases more than ten times. We then present how to mathematically guarantee that the accuracy of the QoIs computed from the reduced f is preserved during the compression. We show that the error in the XGC density can be kept under a user-specified tolerance over 1000 timesteps of simulation using the mathematical QoI error control theory of MGARD, whereas traditional error control on the data to be reduced does not guarantee the accuracy of the QoIs.

Gong, Qian↗

Maintaining a critical spectra within Monteburns for a gas-cooled reactor array by way of control rod manipulation

Our burnup study examined the effect of a predicted critical control rod position on the nuclide predictability of several axial and radial locations within a 4×4 graphite moderated gas cooled reactor fuel cluster geometry. To achieve this, a control rod position estimator (CRPE) tool was developed within the framework of the linkage code Monteburns between the transport code MCNP and depletion code CINDER90, and four methodologies were proposed within the tool for maintaining criticality. Two of the proposed methods used an inverse multiplication approach - where the amount of fissile material in a set configuration is slowly altered until criticality is attained - in estimating the critical control rod position. Another method carried out several MCNP criticality calculations at different control rod positions, then used a linear fit to estimate the critical rod position. The final method used a second-order polynomial fit of several MCNP criticality calculations at different control rod positions to guess the critical rod position. The results showed that consistency in prediction of power densities as well as uranium and plutonium isotopics was mutual among methods within the CRPE tool that predicted critical position consistently well. Finally, while the CRPE tool is currently limited to manipulating a single control rod, future work could be geared toward implementing additional criticality search methodologies along with additional features.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Canonical Wnts, specifically Wnt-10b, show ability to maintain dermal papilla cells

Highlights: •First report on effects of various Wnts on DP cells. •Wnt-10b promoted trichogenesis, while Wnt-3a showed to a limited extent. •Canonical Wnts, specifically Wnt-10b, is important for DP cells maintenance. -- Abstract: Although Wnts are expressed in hair follicles (HFs) and considered to be crucial for maintaining dermal papilla (DP) cells, the functional differences among them remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, 5a, 10b, 11) on the proliferation of mouse-derived primary DP cells in vitro as well as their trichogenesis-promoting ability using an in vivo skin reconstitution protocol. Wnt-10b promoted cell proliferation and trichogenesis, while Wnt-3a showed those abilities to a limited extent, and Wnt-5a and 11 had no effects. Furthermore, we investigated the effects of these Wnts on cultured DP cells obtained from versican-GFP transgenic mice and found that Wnt-10b had a potent ability to sustain their GFP-positivity. These results suggest that canonical Wnts, specifically Wnt-10b, play important roles in the maintenance of DP cells and trichogenesis.

60 APPLIED LIFE SCIENCES↗

HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation

Mitochondria undergo fusion and fission in response to various metabolic stresses. Growing evidences have suggested that the morphological change of mitochondria by fusion and fission plays a critical role in protecting mitochondria from metabolic stresses. Here, we showed that hypoxia treatment could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6 deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus protecting mitochondrial connectivity from hypoxic stress. - Highlights: • Hypoxic stress induces the interaction between HDAC6 and MFN2. • Hypoxic stress activates MARCH5 in HDAC6 deficient cells to degrade MFN2. • HDAC6 is required to maintain mitochondrial connectivity under hypoxia. • MARCH5 is increased and promotes the degradation of MFN2 in HDAC6 KO ALS mice.

60 APPLIED LIFE SCIENCES↗

JNK-associated scattered growth of YD-10B oral squamous carcinoma cells while maintaining the epithelial phenotype

Cell scattering of epithelial carcinoma cancer cells is one of the critical event in tumorigenesis. Cells losing epithelial cohesion detach from aggregated epithelial cell masses and may migrate to fatal organs through metastasis. The present study investigated the molecular mechanism by which squamous cell carcinoma cells grow scattered at the early phase of transformation while maintaining the epithelial phenotype. We studied YD-10B cells, which are established from human oral squamous cell carcinoma, because the cells grow scattered without the development of E-cadherin junctions (ECJs) under routine culture conditions despite the high expression of functional E-cadherin. The functionality of their E-cadherin was demonstrated in that YD-10B cells developed ECJs, transiently or persistently, when they were cultured on substrates coated with a low amount of fibronectin or to confluence. The phosphorylation of JNK was up-regulated in YD-10B cells compared with that in human normal oral keratinocyte cells or human squamous cell carcinoma cells, which grew aggregated along with well-organized ECJs. The suppression of JNK activity induced the aggregated growth of YD-10B cells concomitant with the development of ECJs. These results indicate for the first time that inherently up-regulated JNK activity induces the scattered growth of the oral squamous cell carcinoma cells through down-regulating the development of ECJ despite the expression of functional E-cadherin, a hallmark of the epithelial phenotype. - Highlights: • JNK dissociates YD-10B oral squamous cell carcinoma cells. • JNK suppresses the development of E-cadherin junctions of oral carcinoma cells. • Suppression of JNK activity reverses the scattered growth of oral carcinoma cells.

60 APPLIED LIFE SCIENCES↗

The forkhead-like transcription factor (Fhl1p) maintains yeast replicative lifespan by regulating ribonucleotide reductase 1 (RNR1) gene transcription

In eukaryotes, numerous genetic factors contribute to the lifespan including metabolic enzymes, signal transducers, and transcription factors. As previously reported, the forkhead-like transcription factor (FHL1) gene was required for yeast replicative lifespan and cell proliferation. To determine how Fhl1p regulates the lifespan, we performed a DNA microarray analysis of a heterozygous diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which were then screened for lifespan-regulating activity. We identified the ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative lifespan. RNR1 encodes a large subunit of the RNR complex, which consists of two large (Rnr1p/Rnr3p) and two small (Rnr2p/Rnr4p) subunits. Heterozygous deletion of FHL1 reduced transcription of RNR1 and RNR3, but not RNR2 and RNR4. Chromatin immunoprecipitation showed that Fhl1p binds to the promoter regions of RNR1 and RNR3. Cells harboring an RNR1 deletion or an rnr1-C428A mutation, which abolishes RNR catalytic activity, exhibited a short lifespan. In contrast, cells with a deletion of the other RNR genes had a normal lifespan. Overexpression of RNR1, but not RNR3, restored the lifespan of the heterozygous FHL1 mutant to the wild-type (WT) level. The Δfhl1/FHL1 mutant conferred a decrease in dNTP levels and an increase in hydroxyurea (HU) sensitivity. These findings reveal that Fhl1p regulates RNR1 gene transcription to maintain dNTP levels, thus modulating longevity by protection against replication stress. - Highlights: • Fhl1p regulates replicative lifespan and transcription of RNR large subunit genes. • Rnr1p uniquely acts as a lifespan regulator independent of the RNR complex. • dNTP levels modulate longevity by protection against replication stress.

60 APPLIED LIFE SCIENCES↗

Exosomes derived from human umbilical vein endothelial cells promote neural stem cell expansion while maintain their stemness in culture

The neural stem cell (NSC) niche in subventricular zone (SVZ) of adult mammalian brain contains dense vascular plexus, where endothelial cells (ECs) regulate NSCs by releasing plenty of angiocrine factors. However, the role of ECs-derived exosomes, a novel type of mediators of intercellular communications, in the regulation of NSCs remains unclear. In the current study, primary NSCs isolated from embryonic mouse brains form more neurospheres when cultured in the presence of human umbilical vein endothelial cells (HUVECs). The supportive role of ECs in the coculture was significantly attenuated when GW4869, a blocker of exosome formation, was included, suggesting that HUVECs-derived exosomes played a significant role in supporting NSCs. In order to investigate the role of ECs-derived exosomes on NSCs, we collected exosomes from HUVECs. We found that HUVECs-derived exosomes could significantly promote the formation of neurospheres by primary murine NSCs. EdU incorporation and TUNEL assays indicated that the proliferation of NSCs increased while apoptosis decreased when cultured in the presence of HUVECs-derived exosomes. NSCs incubated with the HUVECs-derived exosomes maintained their potential of multi-lineage differentiation potentials. The expression of stemness-related genes was up-regulated. These data suggested that ECs-derived exosomes could play an importantly role in NSC niche, and they might be used as a reagent for ex vivo NSC amplification for medical application.

60 APPLIED LIFE SCIENCES↗

The UBA domain of SnRK1 promotes activation and maintains catalytic activity

Highlights: • SnRK1 α-subunits possess a UBA domain following its kinase domain (KD). • The UBA enhances activating phosphorylation by SnRK1 upstream kinase. • The UBA maintains catalytic activity over time, in contrast to KD-only. • SnRK1 regulation by UBA is distinct from AMPK regulation by the orthologous AID. Sucrose non-fermenting 1-related protein kinase 1 (SnRK1) is a central metabolic regulator and the plant orthologue of the mammalian AMP-activated protein kinase (AMPK); both are energy-sensing heterotrimeric enzymes comprising a catalytic α- and regulatory β- and γ-subunits. α-Subunits contain a serine/threonine kinase domain (KD) at their N-terminus that is immediately followed by a small regulatory domain termed the auto-inhibitory domain (AID) in AMPK and the ubiquitin-associated domain (UBA) in SnRK1. Association of the AID with the AMPK KD inhibits activating phosphorylation of the KD by upstream kinases and promotes dephosphorylation, as well as inhibiting AMPK catalytic activity. Despite these mechanistic insights regarding the AMPK AID, the SnRK1 UBA regulatory implications have not been investigated. Using recombinant protein comprising either the KD-only or KD-AID/KD-UBA, we found that the UBA of SnRK1 acts in a distinct regulatory manner to its orthologous AID of AMPK. Firstly, the plant upstream kinase GRIK2 preferentially phosphorylates the SnRK1 KD-UBA. Secondly, the SnRK1 KD in the absence of the UBA shows near identical initial catalytic activity to the KD-UBA, but in comparison a rapid loss of catalytic activity is observed. Our findings indicate that the role of the UBA in SnRK1 regulation may be more akin to that of the UBA in the mammalian AMPK-related kinases rather than its immediate functional orthologue, AMPK. This study adds to a growing body of work demonstrating the divergent regulatory mechanisms of the orthologous plant SnRK1 and mammalian AMPK.

60 APPLIED LIFE SCIENCES↗

Arginase controls soluble vascular endothelial growth factor receptor 1 (sFlt1) to maintain pregnancy homeostasis

Highlights: • The onset of preeclampsia is likely triggered by increasing sFlt-1. • Administration of sFlt-1 to HUVECs impaired arginase expression and activity. • Administration of arginase inhibitors is a potential treatment for preeclampsia. Excessive soluble fms-like tyrosine kinase-1 (sFlt-1) has been strongly implicated in preeclampsia. An increase in the serum sFlt-1 level occurs before the onset of preeclampsia, and the sFlt-1 level is already higher in women who are predisposed to preeclampsia than in normotensive pregnant women. This study aimed to investigate the relation between arginase and sFlt-1 in the plasma of preeclamptic women and normotensive pregnant women. We suggested that a regulatory mechanism exists that suppresses the level of sFlt-1. The relationship between arginase, one of the nitric oxide (NO) modulators, and sFlt-1 was examined. First, the pregnant women were divided into 4 groups: group 1, sFlt-1 l-cysteine (BEC; arginase inhibitor) impaired sFlt-1 secretion. In contrast, a higher level of sFlt-1 increased arginase expression and activity in HUVECs, as in group 3. These results showed that arginase controlled sFlt-1 elevation to some extent. In conclusion, our results suggest the existence of a mechanism to maintain the level of sFlt-1. Soluble Flt-1 negatively regulated itself against increasing serum sFlt-1 in preeclampsia. Moreover, this study revealed that arginase inhibitors are a potential treatment option for preeclampsia.

60 APPLIED LIFE SCIENCES↗

Chd1p recognizes H3K36Ac to maintain nucleosome positioning near the transcription start site

In Saccharomyces cerevisiae, the ATP-dependent chromatin remodeler, Chd1p, globally affects nucleosome positioning at coding regions, where nucleosomes are specifically and directionally aligned with respect to the transcription start site (TSS). Various auxiliary domains of remodelers play critical roles by performing specialized functions that are unique to the type of remodeler. Here, we report that yeast Chd1p directly binds to acetylated histone H3K36 (H3K36Ac) via its chromodomain, and that H3K36Ac stimulates the nucleosome sliding activity of Chd1p in vitro. Furthermore, we use genome-wide analysis to demonstrate that H3K36Ac promotes the remodeling activity of Chd1p to maintain chromatin stability at the 5′ ends of genes in vivo. Our work linking Chd1p with H3K36Ac provides novel insights into how the nucleosome remodeling activity of Chd1p is controlled near the TSS.

60 APPLIED LIFE SCIENCES↗

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

60 APPLIED LIFE SCIENCES↗