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At least 415 records · Page 23

The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes

The chromatin architecture in promoters is thought to regulate gene expression, but it remains uncertain how most transcription factors (TFs) impact nucleosome position. The MuvB TF complex regulates cell-cycle dependent gene-expression and is critical for differentiation and proliferation during development and cancer. MuvB can both positively and negatively regulate expression, but the structure of MuvB and its biochemical function are poorly understood. Here we determine the overall architecture of MuvB assembly and the crystal structure of a subcomplex critical for MuvB function in gene repression. We find that the MuvB subunits LIN9 and LIN37 function as scaffolding proteins that arrange the other subunits LIN52, LIN54 and RBAP48 for TF, DNA, and histone binding, respectively. Biochemical and structural data demonstrate that MuvB binds nucleosomes through an interface that is distinct from LIN54-DNA consensus site recognition and that MuvB increases nucleosome occupancy in a reconstituted promoter. We find in arrested cells that MuvB primarily associates with a tightly positioned +1 nucleosome near the transcription start site (TSS) of MuvB-regulated genes. These results support a model that MuvB binds and stabilizes nucleosomes just downstream of the TSS on its target promoters to repress gene expression.

59 BASIC BIOLOGICAL SCIENCES↗

MODELING A SPENT NUCLEAR FUEL CASK SEISMIC TEST

The US Department of Energy Spent Fuel and Waste Science and Technology (SFWST) program is planning to conduct a series of full-scale shake table tests to simulate hypothetical earthquake conditions and record the response of surrogate spent nuclear fuel (SNF) assemblies in a canister dry storage system mockup. The shake table motions will represent a range of hypothetical earthquake conditions at hypothetical locations in the continental US to generally define the range of mechanical loads that SNF can be expected to experience during extended dry storage periods. The earthquake conditions will represent seismic hazards in the 2,000-to-20,000-year return period range. The test will use instrumented pressurized water reactor fuel assemblies with surrogate mass inside the fuel rods instead of radioactive fuel pellets. Dummy assemblies with similar mass and dimensions to actual fuel assemblies will occupy the rest of the fuel assembly locations in a SNF canister that holds 32 fuel assemblies. The canister will be located inside a mockup vertical concrete cask. Instrumentation will record the motion of the major components of the complex dynamic system, and strain gauges will be used to record the cladding strain at select locations. Preparations for the test require modeling predictions to identify the range of response of the system and to help select specific earthquake cases to be simulated on the shake table from a large set of potential cases. This paper describes the pretest nonlinear finite element modeling efforts that have been completed to date, including cask system level modeling and fuel assembly modeling in LS-DYNA. The cask system level models are critical for anticipating sliding or tipping of an unanchored cask during the test. The fuel assembly model is needed to estimate the range of cladding strain response and fuel assembly structural response to be expected during the test and cladding strain measurements will be key metrics for model validation and the development of modeling best practices after the test is concluded.

Klymyshyn, Nicholas A.↗

Buckling and vibration analysis of laminated panels using VICONOPT

The analysis aspects of the 23,000-line FORTRAN program VIPASA with constraints and optimization (VICONOPT) are described. Overall stiffness matrices assembled from the earlier exact vibration and instability of plate assemblies including shear and anisotropy (VIPASA) flat plate stiffnesses are optionally coupled by Langrangian multipliers to find critical buckling loads, or natural frequencies of undamped vibration, of prismatic assemblies of anisotropic flat plates with arbitrarily located point supports or simple transverse supporting frames. The longitudunal continuity of typical wing and fuselage panels is closely approximated because the solutions are for the infinitely long structure obtained by repeating a bay and its supports longitudinally. Any longitudinally invariant in-plane plate stresses are permitted, and very rapid solutions are guaranteed by numerous refinements, including multilevel substructuring and a method for repetitive cross sections that is exact for regular polygons used to represent cylinders. Modal displacements and stresses in or between plies of laminated plates are calculated and plotted, with values being recovered at all nodes of substructures. Comparison with usual approximate finite-element methods confirms that, for comparably converged solutions, VICONOPT is typically between 100 and 10(exp 4) times faster.

Kennedy, David↗

Numerical Determination of Critical Conditions for Thermal Ignition

The determination of ignition or thermal explosion in an oxidizing porous body of material, as described by a dimensionless reaction-diffusion equation of the form .tu = .2u + .e-1/u over the bounded region O, is critically reexamined from a modern perspective using numerical methodologies. First, the classic stationary model is revisited to establish the proper reference frame for the steady-state solution space, and it is demonstrated how the resulting nonlinear two-point boundary value problem can be reexpressed as an initial value problem for a system of first-order differential equations, which may be readily solved using standard algorithms. Then, the numerical procedure is implemented and thoroughly validated against previous computational results based on sophisticated path-following techniques. Next, the transient nonstationary model is attacked, and the full nonlinear form of the reaction-diffusion equation, including a generalized convective boundary condition, is discretized and expressed as a system of linear algebraic equations. The numerical methodology is implemented as a computer algorithm, and validation computations are carried out as a prelude to a broad-ranging evaluation of the assembly problem and identification of the watershed critical initial temperature conditions for thermal ignition. This numerical methodology is then used as the basis for studying the relationship between the shape of the critical initial temperature distribution and the corresponding spatial moments of its energy content integral and an attempt to forge a fundamental conjecture governing this relation. Finally, the effects of dynamic boundary conditions on the classic storage problem are investigated and the groundwork is laid for the development of an approximate solution methodology based on adaptation of the standard stationary model.

Luo, W.↗

Pitch Variation Experiments in Water-Moderated Square-Pitched U(6.9)O 2 Fuel Rod Lattices with Fuel to Water Volume Ratios Spanning 0.08 to 0.67

The US Department of Energy (DOE) Nuclear Energy Research Initiative funded the design and construction of the Seven Percent Critical Experiment (7uPCX) at Sandia National Laboratories. The start-up of the experiment facility and the execution of the experiments described here were funded by the DOE Nuclear Criticality Safety Program. The 7uPCX is designed to investigate critical systems with fuel for light water reactors in the enrichment range above 5% 235 U. The 7uPCX assembly is a water-moderated and -reflected array of aluminum-clad square-pitched U(6.90%)O 2 fuel rods. Other critical experiments performed in the 7uPCX assembly are documented in LEU-COMP-THERM-078, LEU-COMP-THERM-080, LEU-COMPTHERM- 096, LEU-COMP-THERM-097, and LEU-COMP-THERM-101. The twenty-seven critical experiments in this series were performed in 2020 in the SCX at the Sandia Pulsed Reactor Facility. The experiments are grouped by fuel rod pitch. Case 1 is a base case with a pitch of 0.8001 cm and no water holes in the array. Cases 2 through 6 have the same pitch as Case 1 but contain various configurations with water holes, providing slight variations in the fuel-to-water ratio. Similarly, Case 7 is a base case with a pitch of 0.854964 cm and no water holes in the array. Cases 8 through 11 have the same pitch as Case 7 but contain various configurations with water holes. Cases 12 through 15 have a pitch of 1.131512 cm and differ according to the number of water holes in the array, with Case 12 having no water holes. Cases 16 through 19 have a pitch of 1.209102 cm and differ according to number of water holes in the array, with Case 16 having no water holes. Cases 20 through 23 have a pitch of 1.6002 cm and differ according to number of water holes in the array, with Case 20 having no water holes. Cases 24 through 27 have a pitch of 1.709928 cm and differ according to number of water holes in the array, with Case 24 having no water holes. As the experiment case number increases, the fuel-to-water volume ratio decreases.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Assemblies of Conformal Tanks

Assemblies of tanks having shapes that conform to each other and/or conform to other proximate objects have been investigated for use in storing fuels and oxidizers in small available spaces in upper stages of spacecraft. Such assemblies might also prove useful in aircraft, automobiles, boats, and other terrestrial vehicles in which space available for tanks is limited. The basic concept of using conformal tanks to maximize the utilization of limited space is not new in itself: for example, conformal tanks are used in some automobiles to store windshield -washer liquid and coolant that overflows from radiators. The novelty of the present development lies in the concept of an assembly of smaller conformal tanks, as distinguished from a single larger conformal tank. In an assembly of smaller tanks, it would be possible to store different liquids in different tanks. Even if the same liquid were stored in all the tanks, the assembly would offer an advantage by reducing the mechanical disturbance caused by sloshing of fuel in a single larger tank: indeed, the requirement to reduce sloshing is critical in some applications. The figure shows a prototype assembly of conformal tanks. Each tank was fabricated by (1) copper plating a wax tank mandrel to form a liner and (2) wrapping and curing layers of graphite/epoxy composite to form a shell supporting the liner. In this case, the conformal tank surfaces are flat ones where they come in contact with the adjacent tanks. A band of fibers around the outside binds the tanks together tightly in the assembly, which has a quasi-toroidal shape. For proper functioning, it would be necessary to maintain equal pressure in all the tanks.

DeLay, Tom↗

Interaction dynamics of on-orbit construction

Deployment and assembly of large structures in orbit is a critical technology to the overall problem of orbital construction. The attendant large configuration changes of structures will cause significant changes in the dynamic characteristics of the entire system, and perturbation to the orbital dynamics of the spacecraft from which the structures are deployed and/or assembled. To better design structures for deployment and assembly, and to better design controlled deployment/assembly processes, accurate modeling techniques are absolutely essential. The problem of modeling the dynamics of deploying and retrieving beam-like structures from a rotating base was addressed. A methodology for discrete modeling, and a computational procedure were developed. These results give us the capability of understanding and predicting the effects on the overall satellite motion of deploying flexible appendages. This is an initial step towards a general capability of treating axially moving three-dimensional beams. The interaction dynamics of the orbiter, its flexible manipulator, and the structures to be assembled/deployed, as a prerequisite in order to simulate incremental in-space structural construction processes are investigated. Preliminary results so obtained indicate that, as the inertia properties of the flexible large space structure under construction change during the space assembly/construction process, the interaction dynamics undergo significant changes in their characteristics, thus revealing the need for a variety of control strategies throughout construction.

Park, K. C.↗

Effective Utilization of Resources and Infrastructure for a Spaceport Network Architecture

Providing routine, affordable access to a variety of orbital and deep space destinations requires an intricate network of ground, planetary surface, and space-based spaceports like those on Earth (land and sea), in various Earth orbits, and on other extraterrestrial surfaces. Advancements in technology and international collaboration are critical to establish a spaceport network that satisfies the requirements for private and government research, exploration, and commercial objectives. Technologies, interfaces, assembly techniques, and protocols must be adapted to enable mission critical capabilities and interoperability throughout the spaceport network. The conceptual space mission architecture must address the full range of required spaceport services, from managing propellants for a variety of spacecraft to governance structure. In order to accomplish affordability and sustainability goals, the network architecture must consider deriving propellants from in situ planetary resources to the maximum extent possible. Water on the Moon and Mars, Mars' atmospheric CO2, and O2 extracted from lunar regolith are examples of in situ resources that could be used to generate propellants for various spacecraft, orbital stages and trajectories, and the commodities to support habitation and human operations at these destinations. The ability to use in-space fuel depots containing in situ derived propellants would drastically reduce the mass required to launch long-duration or deep space missions from Earth's gravity well. Advances in transformative technologies and common capabilities, interfaces, umbilicals, commodities, protocols, and agreements will facilitate a cost-effective, safe, reliable infrastructure for a versatile network of Earth- and extraterrestrial spaceports. Defining a common infrastructure on Earth, planetary surfaces, and in space, as well as deriving propellants from in situ planetary resources to construct in-space propellant depots to serve the spaceport network, will reduce exploration costs due to standardization of infrastructure commonality and reduction in number and types of interfaces and commodities.

Gill, Tracy↗

Pitch Variation Experiments in Water-Moderated Square-Pitched U(6.90)O 2 Fuel Rod Lattices with Fuel to Water Volume Ratios Spanning 0.08 to 0.67

The US Department of Energy (DOE) Nuclear Energy Research Initiative funded the design and construction of the Seven Percent Critical Experiment (7uPCX) at Sandia National Laboratories. The start-up of the experiment facility and the execution of the experiments described here were funded by the DOE Nuclear Criticality Safety Program. The 7uPCX is designed to investigate critical systems with fuel for light water reactors in the enrichment range above 5 % 235 U. The 7uPCX assembly is a water-moderated and -reflected array of aluminum-clad square-pitched U(6.90 %)O 2 fuel rods. Other critical experiments performed in the 7uPCX assembly are documented in LEU-COMP-THERM-078, LEU-COMP-THERM-080, LEU-COMPTHERM- 096, LEU-COMP-THERM-097, and LEU-COMP-THERM-101. The fuel used in these experiments was fabricated using unirradiated 6.90 % enriched UO 2 fuel pellets from fuel elements designed to be used in the internal nuclear superheater section of the Pathfinder boiling water reactor operated in South Dakota by the Northern States Power Company in the 1960s. The fuel elements were obtained from The Pennsylvania State University where they had been stored for many years. The fuel pellets in those fuel elements were removed from the original Incoloy cladding and reclad in 3003 aluminum tubes and end caps for use in the experiments reported here. The purpose of these experiments was to measure the effects of decreasing the fuel-to-water volume ratio on the critical array size. This was accomplished by removing fuel rods from fully fueled configurations, effectively increasing the pitch of the fuel arrays in the assembly. The fuel rod pitch variations provided assembly configurations that ranged from strongly undermoderated to slightly overmoderated.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Signal sequences target enzymes and structural proteins to bacterial microcompartments and are critical for microcompartment formation

ABSTRACT Spatial organization of pathway enzymes has emerged as a promising tool to address several challenges in metabolic engineering, such as flux imbalances and off-target product formation. Bacterial microcompartments (MCPs) are a spatial organization strategy used natively by many bacteria to encapsulate metabolic pathways that produce toxic, volatile intermediates. Several recent studies have focused on engineering MCPs to encapsulate heterologous pathways of interest, but how this engineering affects MCP assembly and function is poorly understood. In this study, we investigated the role of signal sequences, short domains that target proteins to the MCP core, in the assembly of 1,2-propanediol utilization (Pdu) MCPs. We characterized two novel Pdu signal sequences on the structural proteins PduM and PduB, which constitute the first report of metabolosome signal sequences on structural proteins rather than enzymes. We then explored the role of enzymatic and structural Pdu signal sequences on MCP assembly by deleting their encoding sequences from the genome alone and in combination. Deleting enzymatic signal sequences decreased the MCP formation, but this defect could be recovered in some cases by overexpressing genes encoding the knocked-out signal sequence fused to a heterologous protein. By contrast, deleting structural signal sequences caused similar defects to knocking out the genes encoding the full-length PduM and PduB proteins. Our results contribute to a growing understanding of how MCPs form and function in bacteria and provide strategies to mitigate assembly disruption when encapsulating heterologous pathways in MCPs. IMPORTANCE Spatially organizing biosynthetic pathway enzymes is a promising strategy to increase pathway throughput and yield. Bacterial microcompartments (MCPs) are proteinaceous organelles that many bacteria natively use as a spatial organization strategy to encapsulate niche metabolic pathways, providing significant metabolic benefits. Encapsulating heterologous pathways of interest in MCPs could confer these benefits to industrially relevant pathways. Here, we investigate the role of signal sequences, short domains that target proteins for encapsulation in MCPs, in the assembly of 1,2-propanediol utilization (Pdu) MCPs. We characterize two novel signal sequences on structural proteins, constituting the first Pdu signal sequences found on structural proteins rather than enzymes, and perform knockout studies to compare the impacts of enzymatic and structural signal sequences on MCP assembly. Our results demonstrate that enzymatic and structural signal sequences play critical but distinct roles in Pdu MCP assembly and provide design rules for engineering MCPs while minimizing disruption to MCP assembly.

Johnson, Elizabeth R. (ORCID:0000000179236881)↗

Progress on the reevaluation and validation of the n+233U neutron cross sections

The set of 233 U resonance parameters of the ENDF/B-VIII.0 nuclear data library was adopted from the previous ENDF/B-VII.1 evaluation using the external levels to update the thermal values. Adoption of IAEA 2017 thermal standards ( σ f = 533.0 ± 2.2 b, σ c = 44.9 ± 0.9 b, and ν ‾ tot = 2.487 ± 0.011 ) and of the IAEA-recommended thermal-neutron induced prompt fission neutron spectrum (PFNS) with average PFNS energy of 2.030 ± 0.013 MeV requires a re-evaluation of 233 U neutron cross sections in the resolved resonance region. A newly produced evaluation is being tested on benchmarks carefully selected from the Handbook of International Criticality Safety Benchmark Experiments (ICSBEP) which are highly sensitive to 233 U data. An important goal of this work was to eliminate the strong negative gradient of the calculated effective multiplication factors with respect to the epithermal fission fraction observed in the validation of the ENDF/B-VIII.0 library for those assemblies. A significant improvement in integral performance of critical 233 U solutions is observed for the newly proposed evaluation. Further work addressing the fast neutron region is needed.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Partially-Reflected Water-Moderated Square-Pitched U(6.90)O 2 Fuel Rod Lattices with 0.52 Fuel to Water Volume Ratio (0.855 CM Pitch)

The US Department of Energy (DOE) Nuclear Energy Research Initiative funded the design and construction of the Seven Percent Critical Experiment (7uPCX) at Sandia National Laboratories. The start-up of the experiment facility and the execution of the experiments described here were funded by the DOE Nuclear Criticality Safety Program. The 7uPCX is designed to investigate critical systems with fuel for light water reactors in the enrichment range above 5 % 235 U. The 7uPCX assembly is a water-moderated and -reflected array of aluminum-clad square-pitched U(6.90 %)0 2 fuel rods. Other critical experiments performed in the 7uPCX assembly are documented in LEU-COMP-THERM-078, LEU-COMP-THERM-080, LEU-COMP-THERM-096, and LEU-COMP-THERM-097.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Parametric analysis of RF communications and tracking systems for manned space stations

System performance, system interface compatibility, and system management and operations are analyzed for external and internal communications provided by the modular space station. Mathematical models are utilized to evaluate performances of the various communication links between the MSS and the tracking and data relay satellites, the shuttle, and the ground stations. Communication control design requirements are determined from overall MSS control design and checkout requirements are developed in a related systems study. Parallel design efforts consider equipment configurations for the external communication assembly baseband and the internal communication assembly to accommodate signal transfer and control. The recommended baseline design considers also interfaces between equipment groups and the critical functional and signal characteristics of these interfaces. The data processing assembly has direct communication circuits to the external communication assembly and the control interface is provided via a digital data bus and a remote acquisition and control unit.

Source record↗

Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry

Tousled-like kinases (TLKs) are nuclear serine-threonine kinases essential for genome maintenance and proper cell division in animals and plants. A major function of TLKs is to phosphorylate the histone chaperone proteins ASF1a and ASF1b to facilitate DNA replication-coupled nucleosome assembly, but how TLKs selectively target these critical substrates is unknown. Here, we show that TLK2 selectivity towards ASF1 substrates is achieved in two ways. First, the TLK2 catalytic domain recognizes consensus phosphorylation site motifs in the ASF1 C-terminal tail. Second, a short sequence at the TLK2 N-terminus docks onto the ASF1a globular N-terminal domain in a manner that mimics its histone H3 client. Disrupting either catalytic or non-catalytic interactions through mutagenesis hampers ASF1 phosphorylation by TLK2 and cell growth. Our results suggest that the stringent selectivity of TLKs for ASF1 is enforced by an unusual interaction mode involving mutual recognition of a short sequence motifs by both kinase and substrate.

59 BASIC BIOLOGICAL SCIENCES↗

Insights into the mechanism of SARS-CoV-2 main protease autocatalytic maturation from model precursors

A critical step for SARS-CoV-2 assembly and maturation involves the autoactivation of the main protease (MPro WT ) from precursor polyproteins. Upon expression, a model precursor of MPro WT mediates its own release at its termini rapidly to yield a mature dimer. A construct with an E290A mutation within MPro exhibits time dependent autoprocessing of the accumulated precursor at the N-terminal nsp4/nsp5 site followed by the C-terminal nsp5/nsp6 cleavage. In contrast, a precursor containing E290A and R298A mutations (MPro M ) displays cleavage only at the nsp4/nsp5 site to yield an intermediate monomeric product, which is cleaved at the nsp5/nsp6 site only by MPro WT . MPro M and the catalytic domain (MPro 1-199 ) fused to the truncated nsp4 region also show time-dependent conversion in vitro to produce MPro M and MPro 1-199 , respectively. The reactions follow first-order kinetics indicating that the nsp4/nsp5 cleavage occurs via an intramolecular mechanism. These results support a mechanism involving an N-terminal intramolecular cleavage leading to an increase in the dimer population and followed by an intermolecular cleavage at the C-terminus. Thus, targeting the predominantly monomeric MPro precursor for inhibition may lead to the identification of potent drugs for treatment.

59 BASIC BIOLOGICAL SCIENCES↗

Lessons from Testing the First Three US HL-LHC Cryo-Assemblies at FNAL

The US High-Luminosity LHC Accelerator Upgrade Project (AUP) collaborates with CERN to deliver 10 cryo-assemblies for the High-Luminosity LHC upgrade at CERN. Those comprise the Q1/Q3 quadrupole optical elements in the accelerator and are based on Nb3Sn technology, for the first time in a large particle accelerator. So far three cryo-assemblies were tested at the Fermilab’s horizontal magnet test facility, specifically redesigned to serve those needs. This work gives an overview of the facility and its necessary evolution as the campaign progressed; main results and observations from the cryo-assembly tests are presented and discussed in the context of overall performance and expectations toward the completion of efforts. Lessons learned after multiple cryo-assembly tests by the same team are critical to ensure continuous success of the whole enterprise – those are openly shared.

Stoynev, Stoyan [Fermilab]↗

Predicting Building Envelope Construction from In-Situ Thermal Testing

When embarking on a retrofit of a building envelope, it is critical to understand the composition of its assembly. This practice is currently done by destructive and invasive material testing or demolition, which is sometimes not possible when in historic or protected buildings. To address this problem, in-situ thermal testing can be utilized along with machine learning classification algorithms to infer the composition of an assembly. In this paper, a proof-of-concept K-nearest neighbors classification model is developed to classify assembly composition from effective thermal resistance, effective thermal mass, and assembly cladding. This model was trained and tested utilizing a synthetic dataset producing an F1-score of 94.6%. This model was also validated with experimental data from a 100-year old wall assembly, confirming the model’s real-world validity. The paper presents a framework for inferring as-built envelope assemblies, all without having to damage or disturb the building and its occupants.

Pilet, Tyler J.↗