Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “replication”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

SuperHERO (Super - High Energy Replicated Optics) Balloon Mission Concept

The SuperHERO hard-x-ray telescope is a proposed high-angular resolution successor to Marshall Space Flight Center’s (MSFC) successful High Energy Replicated Optic (HERO) and the HERO to Explore the Sun (HEROES) balloon missions. By utilizing recent advancements in MSFC’s replicated full shell, NiCo x-ray optic technology, SuperHERO will achieve its technical goal of demonstrating better than 10 arcseconds (arcsecs) angular resolution in half-power diameter (HPD) on a balloon platform. This represents a 6-fold improvement to the current state-of-the-art resolution for hard-x-ray, astrophysical telescopes and will allow for the observation of the high-energy-universe in unprecedented spatial detail. The SuperHERO balloon observatory will consist of seven coaligned, identical telescopes with a total focal length of 12-meters. Each telescope will pair a Mirror Module Assembly (MMA) comprised of NiCo shell optics matched to a CdTe Double-sided Strip Detector (CdTe-DSD) plane provided by iMAGINE-X Inc. and Kavli Institute for the Physics and Mathematics of the Universe (Kavli-IPMU). Iridium coating applied directly to each shell will boost reflectivity into the hard-x-ray regime. Employing additional high-heritage technology, SuperHERO will have an open-truss carbon-composite gondola similarly used on the XL-Calibur balloon mission and will use the Wallops Arc-Second Pointer (WASP) system for attitude control

NickThomas↗
DOE OSTI2022

Development of Accelerated Steady-state Test Capsule Experiments to Replicate EBR-II Fuel Behavior Using BISON Fuel Performance Analysis

Here in this work, BISON fuel performance calculations were performed to predict the fuel behavior of accelerated burnup U-Pu-Zr fuel, with temperature operation conditions of the fuel and the cladding mirroring conditions within EBR-II fuel pins. The temperature operating conditions within the FAST accelerated burnup rods were aimed at replicating EBR-II X447/X447A fuel surface and inner cladding surface temperatures. Due to the FAST capsule design, these temperatures can be replicated with fission rate densities being significantly increased. fuel performance modeling has not been assessed for novel experiments such as accelerated burnup utilizing the FAST capsule within ATR. This is an important step in understanding accelerated irradiation methods as many performance models are empirical models conforming to the results of PIE but do not always include physical models that would represent the changes in irradiation tests.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2026

Impedance Based Fixture Neutralization (FINE) Method to Replicate Field Environments in Laboratory Settings

Test article vibration test responses will vary from one test laboratory to another due to differences in shaker and fixture dynamic characteristics. This is also seen between the field and laboratory due to the differing dynamic characteristics between field assembly loading and boundary conditions compared to the laboratory configuration. This work introduces a technique called Impedance Fixture Neutralization which customizes input forces to cause consistent responses for the Device Under Test across different vibration testing conditions. The customized force neutralizes the dynamic variations between configurations for the Device Under Test. The device responses can be replicated in several situations: when using a different fixture with the same attachment points, when the test article mounting location on the fixture changes, when the force location changes, or any combination of these situations. Impedance Fixture Neutralization uses the uncoupled dynamic characteristics of the test article and excitation fixtures to customize the input thereby causing the same test article responses between two mounting configurations (either field to laboratory or two different laboratory configurations). The application of the technique is shown using an analytical model of a two-beam system and analytically using experimental FRFs from plate and frame component hardware characterization tests. In both cases a device under test is attached to two test fixtures wherein the dynamic differences in the configurations are neutralized.

Laboratory↗
DOE OSTI2018

Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum

Highlights: • PfCAF1 interacts with several proteins including PfCAF2, Histones and PfHP1. • PfCAF1 and PfHP1 share similar binding sites in the genome of P. falciparum during ring and schizont stages. • PfCAF1 co-localizes with newly synthesized histone mark H3K56Ac. • PfCAF1 expression upregulates after DNA damage along with PCNA. Nucleosome assembly in P. falciparum could be the key process in maintaining its genomic integrity as DNA replicates more than once per cell cycle during several stages of its life cycle. Here, we report the functional characterization of P. falciparum chromatin assembly factor 1 (CAF1), which interacts with several proteins namely PfCAF2, Histones, PfHP1 and others. Consistent with the above findings, we demonstrate the presence of PfCAF1 at the telomeric repeat regions, central and subtelomeric var genes of multiple var gene family along with PfHP1. Further, we report the upregulation of PfCAF1 after treatment with genotoxic agents like MMS and HU. Together, these findings establish role of PfCAF1 in heterochromatin maintenance and as histone chaperone in nucleosome assembly and DNA damage repair.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6

Significance The loading of the core Mcm2-7 helicase onto origin DNA is essential for the formation of replication forks and genomic stability. Here, we report two cryo-electron microscopy (cryo-EM) structures that capture helicase loader–helicase complexes just prior to DNA insertion. These pre-loading structures, combined with a computational simulation of the dynamic transition from the pre-loading state to the loaded state, provide crucial insights into the mechanism required for topologically linking the helicase to DNA. The helicase loading system is highly conserved from yeast to human, which means that the molecular principles described here for the yeast system are likely applicable to the human system.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Chlamydomonas CHT7 is involved in repressing DNA replication and mitotic genes during synchronous growth

In the green alga Chlamydomonas reinhardtii, regulation of the cell cycle in response to external cues is critical for survival in a changing environment. The loss of the nuclear COMPROMISED HYDROLYSIS OF TRIACYLGLYCEROLS 7 (CHT7) protein affects the expression of many genes especially in response to nitrogen availability. Cells lacking CHT7 exhibit abnormal cell morphology following nitrogen deprivation and fail to resume normal cell division after N resupply. To investigate the function of CHT7 in the regulation of cell cycle-related pathways, cells were synchronized, and RNA-seq analysis was performed during various stages of the cell cycle. In the cht7 mutant following nitrogen deprivation, the cells were not dividing, but a subset of cell cycle genes involved in DNA replication and mitosis were found to be derepressed, suggesting that the CHT7 protein plays a role in cell cycle regulation that is opposite to that of the mitotic cyclin-dependent kinases. Furthermore, genes for cell wall synthesis and remodeling were found to be abnormally induced in nondividing cht7 cells; this misregulation may deplete cellular resources and thus contribute to cell death following nitrogen deprivation. Lastly, 43 minimally characterized kinases were found to be highly misregulated in cht7. Further analysis suggested that some of these CHT7-regulated kinases may be related to the MAP3K and Aurora-like kinases, while others are unique. Together, these results suggest a role of CHT7 in transcriptional regulation of the cell cycle and reveal several pathways and genes whose expression appears to be subject to a CHT7-mediated regulatory network.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Replicated computational results (RCR) report for "BLIS: A framework for rapidly instantiating BLAS functionality"

“BLIS: A Framework for Rapidly Instantiating BLAS Functionality” includes single-platform BLIS performance results for both level-2 and level-3 operations that is competitive with OpenBLAS, ATLAS, and Intel MKL. A detailed description of the configuration used to generate the performance results was provided to the reviewer by the authors. All the software components used in the comparison were reinstalled and new performance results were generated and compared to the original results. After completing this process, the published results are deemed replicable by the reviewer.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Decoding Cancer Variants of Unknown Significance for Helicase–Nuclease–RPA Complexes Orchestrating DNA Repair During Transcription and Replication

All tumors have DNA mutations, and a predictive understanding of those mutations could inform clinical treatments. However, 40% of the mutations are variants of unknown significance (VUS), with the challenge being to objectively predict whether a VUS is pathogenic and supports the tumor or whether it is benign. To objectively decode VUS, we mapped cancer sequence data and evolutionary trace (ET) scores onto crystallography and cryo-electron microscopy structures with variant impacts quantitated by evolutionary action (EA) measures. As tumors depend on helicases and nucleases to deal with transcription/replication stress, we targeted helicase–nuclease–RPA complexes: (1) XPB-XPD (within TFIIH), XPF-ERCC1, XPG, and RPA for transcription and nucleotide excision repair pathways and (2) BLM, EXO5, and RPA plus DNA2 for stalled replication fork restart. As validation, EA scoring predicts severe effects for most disease mutations, but disease mutants with low ET scores not only are likely destabilizing but also disrupt sophisticated allosteric mechanisms. For sites of disease mutations and VUS predicted to be severe, we found strong co-localization to ordered regions. Rare discrepancies highlighted the different survival requirements between disease and tumor mutations, as well as the value of examining proteins within complexes. In a genome-wide analysis of 33 cancer types, we found correlation between the number of mutations in each tumor and which pathways or functional processes in which the mutations occur, revealing different mutagenic routes to tumorigenesis. We also found upregulation of ancient genes including BLM, which supports a non-random and concerted cancer process: reversion to a unicellular, proliferation-uncontrolled, status by breaking multicellular constraints on cell division. Together, these genes and global analyses challenge the binary “driver” and “passenger” mutation paradigm, support a gradient impact as revealed by EA scoring from moderate to severe at a single gene level, and indicate reduced regulation as well as activity. The objective quantitative assessment of VUS scoring and gene overexpression in the context of functional interactions and pathways provides insights for biology, oncology, and precision medicine.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing early-structure and early-testing (ESET) experiments by many laboratories. By employing an efficient VS protocol to examine protein-protein interfaces (PPIs) and allosteric interactions, we identify ligand binding sites beyond active sites, leveraging in silico advances for molecular docking and modeling to screen PPIs and multiple targets. A diverse 3,174 compound ESET library combines Diamond Light Source DSI-poised, Protein Data Bank fragments, and FDA-approved drugs to span relevant chemotypes and facilitate downstream hit evaluation efficiency for academic laboratories. Two VS per library and multiple ranked ligand binding poses enable target testing for several DDR targets. This GL library and protocol can thus strategically probe multiple DDR network targets and identify readily available compounds for early structural and activity testing to overcome bottlenecks that can limit timely breakthrough drug discoveries. By testing accessible compounds to dissect multi-functional DDRs and suggesting inhibitor mechanisms from initial docking, the GL approach may enable more groups to help accelerate discovery, suggest new sites and compounds for challenging targets including emerging biothreats and advance cancer biology for future precision medicine clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1998

Replication-deficient adenovirus vector transfer of gfp reporter gene into supraoptic nucleus and subfornical organ neurons

The present studies used defined cells of the subfornical organ (SFO) and supraoptic nuclei (SON) as model systems to demonstrate the efficacy of replication-deficient adenovirus (Ad) encoding green fluorescent protein (GFP) for gene transfer. The studies investigated the effects of both direct transfection of the SON and indirect transfection (i.e., via retrograde transport) of SFO neurons. The SON of rats were injected with Ad (2 x 10(6) pfu) and sacrificed 1-7 days later for cell culture of the SON and of the SFO. In the SON, GFP fluorescence was visualized in both neuronal and nonneuronal cells while only neurons in the SFO expressed GFP. Successful in vitro transfection of cultured cells from the SON and SFO was also achieved with Ad (2 x 10(6) to 2 x 10(8) pfu). The expression of GFP in in vitro transfected cells was higher in nonneuronal (approximately 28% in SON and SFO) than neuronal (approximately 4% in SON and 10% in SFO) cells. The expression of GFP was time and viral concentration related. No apparent alterations in cellular morphology of transfected cells were detected and electrophysiological characterization of transfected cells was similar between GFP-expressing and nonexpressing neurons. We conclude that (1) GFP is an effective marker for gene transfer in living SON and SFO cells, (2) Ad infects both neuronal and nonneuronal cells, (3) Ad is taken up by axonal projections from the SON and retrogradely transported to the SFO where it is expressed at detectable levels, and (4) Ad does not adversely affect neuronal viability. These results demonstrate the feasibility of using adenoviral vectors to deliver genes to the SFO-SON axis. Copyright 1998 Academic Press.

NASA Discipline Regulatory Physiology↗
DOE OSTI2016

Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein A

Replication protein A (RPA) is an essential single-stranded DNA (ssDNA)-binding protein that initiates the DNA damage response pathway through protein–protein interactions (PPIs) mediated by its 70N domain. The identification and use of chemical probes that can specifically disrupt these interactions is important for validating RPA as a cancer target. A high-throughput screen (HTS) to identify new chemical entities was conducted, and 90 hit compounds were identified. From these initial hits, an anthranilic acid based series was optimized by using a structure-guided iterative medicinal chemistry approach to yield a cell-penetrant compound that binds to RPA70N with an affinity of 812 nm. This compound, 2-(3- (N-(3,4-dichlorophenyl)sulfamoyl)-4-methylbenzamido)benzoic acid (20 c), is capable of inhibiting PPIs mediated by this domain.

Patrone, James D.↗
DOE OSTI2021

Entanglement wedge cross section inequalities from replicated geometries

We generalize the constructions for the multipartite reflected entropy in order to construct spacetimes capable of representing multipartite entanglement wedge cross sections of differing party number as Ryu-Takayanagi surfaces on a single replicated geometry. We devise a general algorithm for such constructions for arbitrary party number and demonstrate how such methods can be used to derive novel inequalities constraining mulipartite entanglement wedge cross sections.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2016

Pond Crash Forensics: Presumptive identification of pond crash agents by next generation sequencing in replicate raceway mass cultures of Nannochloropsis salina

Productivity of algal mass culture can be severely reduced by contaminating organisms. It is, therefore, important to identify contaminants, determine their effect on productivity and, ultimately, develop countermeasures against such contamination. In this paper, we utilized microbiome analysis by second-generation sequencing of small subunit rRNA genes to characterize the predator and pathogen burden of open raceway cultures of Nannochloropsis salina. Samples were analyzed from replicate raceways before and after crashes. In one culture cycle, we identified two algivorous species, the rotifer Brachionus and gastrotrich Chaetonotus, the presence of which may have contributed to the loss of algal biomass. In the second culture cycle, the raceways were treated with hypochlorite in an unsuccessful attempt to interdict the crash. Finally, our analyses were shown to be an effective strategy for the identification of the biological contaminants and the characterization of intervention strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease

Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. Here, we demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A Task-Optimized Neural Network Replicates Human Auditory Behavior, Predicts Brain Responses, and Reveals a Cortical Processing Hierarchy

A core goal of auditory neuroscience is to build quantitative models that predict cortical responses to natural sounds. Reasoning that a complete model of auditory cortex must solve ecologically relevant tasks, we optimized hierarchical neural networks for speech and music recognition. The best-performing network contained separate music and speech pathways following early shared processing, potentially replicating human cortical organization. The network performed both tasks as well as humans and exhibited human-like errors despite not being optimized to do so, suggesting common constraints on network and human performance. The network predicted fMRI voxel responses substantially better than traditional spectrotemporal filter models throughout auditory cortex. It also provided a quantitative signature of cortical representational hierarchy—primary and non-primary responses were best predicted by intermediate and late network layers, respectively. Here the results suggest that task optimization provides a powerful set of tools for modeling sensory systems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Cardiovirus Leader proteins bind exportins: Implications for virus replication and nucleocytoplasmic trafficking inhibition

Cardiovirus Leader proteins (L{sub X}) inhibit cellular nucleocytoplasmic trafficking by directing host kinases to phosphorylate Phe/Gly-containing nuclear pore proteins (Nups). Resolution of the Mengovirus L{sub M} structure bound to Ran GTPase, suggested this complex would further recruit specific exportins (karyopherins), which in turn mediate kinase selection. Pull-down experiments and recombinant complex reconstitution now confirm that Crm1 and CAS exportins form stable dimeric complexes with encephalomyocarditis virus L{sub E}, and also larger complexes with L{sub E}:Ran. shRNA knockdown studies support this idea. Similar activities could be demonstrated for recombinant L{sub S} and L{sub T} from Theiloviruses. When mutations were introduced to alter the L{sub E} zinc finger domain, acidic domain, or dual phosphorylation sites, there was reduced exportin selection. These regions are not involved in Ran interactions, so the Ran and Crm1 binding sites on L{sub E} must be non-overlapping. The involvement of exportins in this mechanism is important to viral replication and the observation of trafficking inhibition by L{sub E}.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MicroRNA-182 inhibits HCMV replication through activation of type I IFN response by targeting FOXO3 in neural cells

Human cytomegalovirus (HCMV) has led to kinds of clinical disorders and great morbidity worldwide, such as sensorineural hearing loss (SNHL), mental retardation, and developmental delays in immunocompromised individuals. Congenital HCMV infection is a leading cause of birth defects, primarily manifesting as neurological disorders. Previous studies reported that HCMV has evolved a variety of mechanisms to evade the immune system, such as dysregulation of miRNAs. However, reports concerning the role of miRNA in HCMV infection in neural cells are limited. Here, we reported that a host microRNA, miR-182, was significantly up-regulated by HCMV infection in U-251MG and NPCs cells. Subsequently, our results of in vitro and in vivo experiments demonstrated that miR-182 was a positive regulator of interferon regulatory factor 7 (IRF7) by directly targeting FOXO3, resulting in the induction of IFN-I response and suppression of HCMV replication in neural cells. Taken together, our findings provide detailed molecular mechanisms of the antiviral function of miR-182 against HCMV infection in neural cells, and suggest an intrinsic anti-HCMV therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, and these had higher proliferative potential, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γ-H2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.

60 APPLIED LIFE SCIENCES↗