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At least 1,369 records · Page 76

Multimodal spectroscopy of order parameter distributions

We present a multimodal spectroscopic paradigm that enables independent measurement of charge and spin degrees of freedom (DOF) in strongly correlated materials. This spin-based technique probes symmetry-specific Hamiltonian parameters by analyzing how the time delay between applied pulses (τ) affects the response. We demonstrate ways in which charge DOF that couple through the quadrupolar interaction (inversion symmetric) can be independently measured even in the presence of large magnetic noise (inversion asymmetric). The method quantifies both the strength of the interactions and their distribution (noise). We provide protocols to directly and independently measure the distribution of interaction strengths, even when the average value of the interaction is zero. By independently measuring distributions of different forms of disorder, this methodology can elucidate which microscopic symmetry drives a phase transition. Here, we discuss potential applications to study complex phase transitions in strongly interacting quantum materials.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Collective dynamics and defect generation for Wigner crystal ratchets

Here we consider a two-dimensional Wigner crystal coupled to a quasi-one-dimensional asymmetric potential under ac or dc driving. As a function of electron density, substrate strength, and ac amplitude, we find that the system exhibits ordered and disordered pinned and dynamical states. Ratchet effects can appear under an applied ac drive and can be associated with pronounced structural changes from a disordered state to a one-dimensional smecticlike state. We observe a pinned phase, a diodelike ratchet where motion only occurs along the easy direction of the substrate asymmetry, a plastic ratchet where motion occurs in both directions but there is only a net drift in the easy direction, and an elastic ratchet where the system forms a crystal without plastic deformation that can still undergo ratcheting. At high filling, we find that there can be a ratchet reversal in which the net drift is along the hard direction of the substrate asymmetry. For weak disorder, there is an Aubry transition to a floating phase where the ratchet effects are lost. We map out the different dynamical phases as a function of substrate strength, filling, ac amplitude, and ac frequency. The ratchet effect on strong substrates is enhanced by thermal fluctuations, but is destroyed when the fluctuations become too large. Based on our results, we suggest other ways to detect Wigner crystals as well as methods for creating different types of devices to control disordered charge flow.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Department of Energy’s Atmospheric System Research (ASR) Program’s Workshop on the Future of Atmospheric Large Eddy Simulation (LES): Workshop Report

Large-eddy simulation (LES) is used as a tool to understand physical processes such as turbulence, aerosols, clouds, precipitation, radiation, the interactions among all these, and their interactions with the underlying surface. Over the next 10 years, LES will drive fundamental progress in open scientific questions in these areas as LES is increasingly used to gain understanding of complex interacting physical processes involving atmospheric turbulence. This growth will be driven both by scientific demand and the expansion of computational resources needed to conduct LES, and the form that the growth takes will largely be determined by how computational resources are leveraged for scientific gain. In particular, we suggest that computational resources are likely to be leveraged in two separate but not necessarily distinct ways. On one hand, growth in computational resources will allow LES to be made more routine, that is, performed more frequently, while on the other hand, the computational expense (measured in total floating point operations) afforded to individual LES will expand dramatically, allowing simulations to increase in both domain size and resolution as well as physical detail. Current U.S. Department of Energy (DOE) projects such as LES ARM Symbiotic Simulation and Observation Activity (LASSO) are leading the way in conducting routine LES, building large, public databases that are accessible for data science, sensitivity studies, and training for machine learning. LES will also become more routine as it becomes more accessible for individual researchers to address their scientific questions of interest. Scientific questions addressed by LES over the next 10 years are likely to include cloud organization and aggregation; aerosol cloud interactions and atmospheric chemistry (including geo-engineering); urban-scale LES; atmospheric extreme events, ranging from small-scale severe weather to wildfires; and ocean-wave-atmosphere interactions. Further LES-related research will likely grow significantly in areas related to societal impact studies of air quality and extreme weather events, applications to renewable energy forecasting and resource assessment, and aid in decision-making processes. The growth in the use of LES in atmospheric science research will drive the need for better physical process representations (e.g., cloud aerosol microphysics, radiation, and atmospheric chemistry) at the scales resolved by LES. To date, many of the process representations used by LES have been taken directly from coarser-resolution models. Promising methods for LES process representations include superdroplet and quadrature methods for microphysics, 3D approaches for radiation, and better representation of chemistry and aerosol processes. At LES resolution, land-atmosphere interactions for complex terrains, land cover/types, biogeochemistry, and plant canopy models are needed as an improvement beyond traditional and widely used Monin-Obuhkov similarity theory.

54 ENVIRONMENTAL SCIENCES↗

Extreme Efficiency 240 Vac to Load Data Center Power Delivery Topologies and Control

The research explored innovative new circuit topologies and power converter architectures for data center power delivery, from the 240 V ac voltage at the input of a server rack, down to the less than 1 V dc power supply of the latest microprocessors. The research pursued three parallel tracks to increase the power conversion efficiency and to reduce the overall size of the servers: 1) An innovative new ac-dc power converter topology which enables improved efficiency through use of a novel direct step-down topology, well suited for the popular 48V dc power distribution. 2) A new series-stacked power delivery approach for servers comprising a large number of similar loads, such as hard drives in storage servers. The approach greatly reduces the power conversion losses, and achieves efficiency well over 99%. 3) A new family of hybrid switched-capacitor power converters that enable improved efficiency and reduced size through the use of dense ceramic capacitors and new circuit topologies that leverage GaN and low-voltage Si transistor technology. Together, the accomplished research achieved the goal of reducing the power conversion losses in datacenters, thereby reducing greenhouse gas emissions, operating costs, and overall electricity consumption.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Global Observation of Planetary-Scale Waves in UARS HRDI and WINDII MLT Winds

The purpose of this study is to use examine planetary-scale motions in the UARS mesosphere and lower thermospheric data. The actual study was confined to HRDI winds and temperatures, since these observations were more continuous, and spanned the 60-120 km range. Three classes of waves were studied: fast equatorial Kelvin waves, nonmigrating tides, and the midlatitude 2-day wave. The purpose of the Kelvin wave and the 2-day wave studies was to test whether the waves significantly affect the mean flow. Such studies require high-quality spectral definitions in order to derive the wave heat and momentum flux divergence which can act in comination to drive the mean flow. Accordingly, HRDI winds from several special observing campaigns were used for analyses of fast (periods under 5 days) waves. The campaigns are characterized by continuous viewing by HRDI in 2 viewing directions, for periods of 10-12 days. Data sampled in this manner lend themselves quite well to "asynoptic spectral analysis", from which motions with periods as low as one day can be retrieved with relatively minimal aliasing.

Lieberman, Ruth↗

High-fidelity wave data from MarineLabs CoastScout™ buoys supporting WEC demonstration at Scripps Pier

Two MarineLabs CoastScout™ buoys were deployed off La Jolla, California in February 2020 to provide high-resolution wave elevation time series data in support of CalWave Power Technologies’ XWave WEC deployment. The buoys are positioned approximately 300m from a longterm wave monitoring station operated by the Coastal Data Information Program. Both CoastScout hull types showed excellent agreement with the reference Datawell Directional Waverider MkIII (Hs r 2 =0.94, m0 r 2 =0.88). The CoastScout buoys maintained 100% uptime throughout an initial 6- month intercomparison period. CalWave used 5-Hz wave train data from this period to drive physical hardware-in-the-loop tests of the XWave power take-off. Throughout the deployment, the CoastScout buoys will provide near-real-time bulk wave parameters to help CalWave operators safely and efficiently operate the WEC. In post-processing, high-fidelity wave resolution will be used to associate individual waves with onboard measurements from Fiber Bragg Grating strain gauges and external pressure sensors.

16 TIDAL AND WAVE POWER↗

Stripe and bubble ratchets on asymmetric substrates

We show that various nonmonotonic ratchet effects can arise when mesophase pattern-forming systems, which exhibit anisotropic crystal, stripe, and bubble regimes, are coupled to one-dimensional asymmetric substrates under ac driving. The patterns emerge in the absence of a substrate when the ratio of attraction to repulsion is varied for particles with competing short-range attraction and long-range repulsion potentials. In the presence of the substrate, we find that the ratchet efficiency varies nonmonotonically with increasing attraction, depending upon how well the mesophase morphology matches the substrate spacing and periodicity. For strong repulsion, there is a weak but finite ratchet effect, while at intermediate attraction, there is a robust ratchet effect in which the system forms stripes aligned with the substrate symmetry direction. For strong attraction, large bubbles appear that have weak or no ratchet effects when the bubble width exceeds the substrate lattice spacing, causing the bubble to be only weakly coupled to the substrate. For very strong attraction, small bubbles form and undergo a strong ratchet effect with an efficiency that oscillates as a function of ac drive amplitude. Although the small bubble regime is a strongly correlated regime in which each bubble contains many particles, the system behaves as if it is in a single-particle regime since the bubble width is much smaller than the substrate lattice spacing. We map out the different rectification phases as a function of the pattern morphology, substrate strength, and ac drive amplitude. The pronounced ratchet effects that we observe in some regimes can be exploited for pattern sorting in hard and soft matter systems. Published by the American Physical Society 2024

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Using Diel Solute Signals to Assess Ecohydrological Processing in Lotic Systems

Lotic systems are a prominent ecohydrological interface within which complex, coupled interactions occur between ecological, hydrological, and geochemical processes. This chapter reviews the ecological processes driving diel signals in oxygen as well as major nutrients and other trace elements. It discusses how diel signals can be used to evaluate functioning and interactions within stream ecosystems. The chapter considers potential future research directions and outstanding questions still to be addressed by or about diel solute signals and associated processes. High-resolution sensor-based time series and associated tools and conceptual advances are being integrated into environmental management. Quantitative tools to disentangle diel biogeochemically-driven signals from other sources of variability in continuous time series are growing. Theoretical models of diel process dynamics are helping to spur hypothesis generation and new ways of approaching diel signals in lotic systems.

Kurz, Marie↗

Thermal-Epithermal eXperiments – Hafnium Experiment Performed at the DOE’s National Criticality Experiments Research Center (NCERC)

The Thermal-Epithermal eXperiments (TEX) – Hafnium (TEX-Hf) experiments were completed in October 2022 at the DOE National Criticality Experiments Research Center (NCERC) at the Nevada National Security Site (NNSS). This measurement campaign provides seven unique configurations that can be used to validate the neutron absorption and scattering cross sections of hafnium in a highly enriched uranium (HEU) system. Hafnium is a strong neutron absorber important for marine propulsion systems. Mike Zerkle of the Naval Nuclear Laboratory (NNL) states, “The experiments were requested by Naval Reactors to provide a suite of unclassified, clean, and well-characterized benchmarks to drive improvements to hafnium nuclear data.” The experiments were a collaboration between Los Alamos National Laboratory (LANL), Lawrence Livermore National Laboratory (LLNL), and NNL, funded by the Nuclear Criticality Safety Program (NCSP). The Hf was procured directly by NNL and provided for the experiment.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Radiation GRMHD Models of Accretion onto Stellar-mass Black Holes. I. Survey of Eddington Ratios

We summarize results from a survey of radiation-dominated black hole accretion flows across a wide range of mass accretion rates, as well as two values of black hole spin and initial magnetic field geometry. These models apply an algorithm targeting direct solutions to the radiation transport equation in full general relativity and have been enabled by access to modern exascale computing systems. Super-Eddington accretion flows form geometrically thick radiation-pressure-supported disks that drive powerful equatorial outflows. A narrow funnel-shaped photosphere in the inner region results in very low radiative efficiencies in this regime. The structure of near- and sub-Eddington accretion depends on whether there is net vertical magnetic flux at the midplane of the disk. With net flux, the disk forms a thin, dense layer at the midplane surrounded by a magnetically dominated corona, whereas without net flux, the disk remains magnetically dominated everywhere. Although none of our models achieve the magnetically arrested disk regime, those with net vertical flux and a rapidly spinning black hole still produce powerful relativistic jets. Our calculations adopt simple opacity models (with scalings appropriate to stellar-mass black hole accretion). We discuss the application of our results to observations of X-ray binaries and ultraluminous X-ray sources such as Cyg X-3 and SS433. We also speculate on the application of our super-Eddington models to the interpretation of little red dots recently discovered by JWST.

79 ASTRONOMY AND ASTROPHYSICS↗

The Bearingless Electrical Machine

Electromagnetic bearings allow the suspension of solids. For rotary applications, the most important physical effect is the force of a magnetic circuit to a high permeable armature, called the MAXWELL force. Contrary to the commonly used MAXWELL bearings, the bearingless electrical machine will take advantage of the reaction force of a conductor carrying a current in a magnetic field. This kind of force, called Lorentz force, generates the torque in direct current, asynchronous and synchronous machines. The magnetic field, which already exists in electrical machines and helps to build up the torque, can also be used for the suspension of the rotor. Besides the normal winding of the stator, a special winding was added, which generates forces for levitation. So a radial bearing, which is integrated directly in the active part of the machine, and the motor use the laminated core simultaneously. The winding was constructed for the levitating forces in a special way so that commercially available standard ac inverters for drives can be used. Besides wholly magnetic suspended machines, there is a wide range of applications for normal drives with ball bearings. Resonances of the rotor, especially critical speeds, can be damped actively.

Bichsel, J.↗

High Displacement Solid State Ferroelectric Loudspeaker

A piezoelectric loudspeaker suitable for midrange frequencies uses a dome shaped piezoelectric actuator to a speaker membrane directly is discussed. The dome shaped actuator is made from a reduced and internally biased oxygen wafer, and generates excursion of the apex of the dome in the order of 0.02-0.05 inches when a rated drive voltage of 350 V rms is applied between the convex and the concave surface of the dome shaped actuator. The load capacity exceeds 10 lbs. The edge of the rim of the dome shaped actuator must be free to rock when the dome height varies to ensure low distortion in the loudspeaker. This is achieved by mounting the rim of the dome shaped actuator on a support surface by prestress only. An exceptionally simple design uses a planar speaker membrane with the center part of one side pressed against the rim of a dome shaped actuator by prestress from a stretched latex surround member.

Regan, Curtis R.↗

Flows in the Solar Convection Zone

Flows within the solar convection zone are the primary drivers of the Sun's magnetic activity cycle. Differential rotation stretches out the magnetic field and converts poloidal fields into toroidal fields. Zones of strong radial shear are found at both the surface and at the base of the convection zone (the tachocline). The poleward meridional flow near the surface transports magnetic flux that is observed to reverse the magnetic poles near the time of cycle maxima. The deeper (and as yet unobserved), equatorward meridional flow should carry magnetic flux toward the equator where it reconnects with oppositely directed fields in the other hemisphere. The non-axisymmetric flows (granules, supergranules, and giant cells) also transport magnetic flux but in a more random, diffusive, manner. Supergranules and giant cells also play significant roles in driving the large-scale, axisymmetric flows themselves. The effect of solar rotation on supergranulation produces the shear layer near the surface and enhances the meridional flow. The effect of solar rotation on giant cells should produce the latitudinal differential rotation, the shear in the tachocline, and the meridional circulation. In this presentation I will describe the observed and theorized characteristics of the flows in the solar convection zone and discuss their connections to the solar activity cycle.

Hathaway, D. H.↗

Starshade Rendezvous: Exoplanet Sensitivity and Observing Strategy

Launching a starshade to rendezvous with the Nancy Grace Roman Space Telescope (Roman) would provide the first opportunity to directly image the habitable zones (HZs) of nearby sunlike stars in the coming decade. A report on the science and feasibility of such a mission was recently submitted to NASA as a probe study concept. The driving objective of the concept is to determine whether Earth-like exoplanets exist in the HZs of the nearest sunlike stars and have biosignature gases in their atmospheres. With the sensitivity provided by this telescope, it is possible to measure the brightness of zodiacal dust disks around the nearest sunlike stars and establish how their population compares with our own. In addition, known gas-giant exoplanets can be targeted to measure their atmospheric metallicity and thereby determine if the correlation with planet mass follows the trend observed in the Solar System and hinted at by exoplanet transit spectroscopy data. We provide the details of the calculations used to estimate the sensitivity of Roman with a starshade and describe the publicly available Python-based source code used to make these calculations. Given the fixed capability of Roman and the constrained observing windows inherent for the starshade, we calculate the sensitivity of the combined observatory to detect these three types of targets, and we present an overall observing strategy that enables us to achieve these objectives.

Andrew Frederic Romero-wolf↗

Spring 2021 Sea Ice Transport in the Southern Beaufort Sea Occurred During Coastal Lead Opening Events

Winds blew a record large portion of the Arctic’s multiyear sea ice (MYI) into the southern Beaufort Sea (SBS) in winter 2021. From early March, a network of buoys from the Sea Ice Dynamic Experiment (SIDEx) tracked the MYI as it drifted across the SBS toward the Chukchi Sea. Transport was episodic as the consolidated ice pack interacted with coastal boundaries and repeatedly fractured. We investigated variability in 2021 MYI transport by relating in situ sea ice drift to remotely sensed coastal lead opening events, which have been associated with increased ice drift speeds in winter. Daily ice concentration data show ten opening events occurred throughout March and April 2021. Opening lasted 1-5 consecutive days as southeasterly winds pushed the SBS ice pack away from coastal boundaries. During opening, the ice pack abruptly accelerated and its response to wind forcing stabilized around free drift conditions, drifting at 2.1 % of wind speeds (median rate of 13.7 km d −1 ). With this efficient wind-to-ice momentum transfer, nearly all (94 %) alongshore MYI transport in March-April 2021 occurred during opening events, which comprised just half of March-April days. Only 6 % of transport occurred during the other half of days without observed opening. On these days, the ice was mostly stationary (median 1.7 km d −1 drift rate, 0.6 % of wind speeds) as northwesterly winds compressed the pack against the coast. Spatiotemporal discontinuities in ice-wind speed ratios were measured across several coastal leads that transected the SIDEx buoy network, providing direct observations of changes in ice drift regime as coastal leads opened. These results quantify the disproportionate contribution of offshore and alongshore winds in breaking the SBS ice pack away from the coast, opening leads, and driving SBS ice transport during spring 2021, highlighting the critical role these episodic events play in consolidation season sea ice drift.

Oceanography↗

Antiferromagnetic memory storage devices from magnetic transition metal dichalcogenides

Switchable antiferromagnetic (AFM) memory devices are provided based on magnetically intercalated transition metal dichalcogenides (TMDs) of the form AxMC2, where A is a magnetic element of stoichiometry x between 0 and 1, M is a transition metal of stoichiometry 1, and C is a chalcogen of stoichiometry 2. Memory storage is achieved by fabricating these materials into crosses of two or more bars and driving DC current pulses along the bars to rotate the AFM order to a fixed angle with respect to the current pulse. Application of current pulses along different bars can switch the AFM order between multiple directions. Standard resistance measurements can detect the orientation of the AFM order as high or low resistance states. The state of the device can be set by the input current pulses, and read-out by the resistance measurement, forming a non-volatile, AFM memory storage bit.

Analytis, James G.↗

Probabilistic Modeling of a Three-Stage Human Landing System Architecture

Space Policy Directive-1 has led to NASA partnerships with commercial entities on procurement which includes the development of the Human Landing System (HLS) [1]. With the goal of delivering human crew to the lunar surface by 2024, system uncertainties become an important obstacle to the maturation of multiple new, driving technologies and mission concepts of the HLS program. As unmitigated uncertainties have previously led to failed development programs, these risks and their impacts must be understood and handled to ensure program success [2]. Sources of uncertainty include novel engine designs and configurations, increased reliance on cryogenic fluid management(CFM), and refueling technologies—which propagate as high-level performance metrics such as overall propellant mass and engine performance. Also, the occurrence of operational uncertainties—e.g. launch conditions or need to abort during the mission—can cause cascading effects on the rest of the mission that are difficult to definitively quantify, and are outside the scope of control. These concrete examples and other occurrences can be categorized as either epistemic or aleatory uncertainties.Epistemic uncertainty arises due to a lack of knowledge and can be alleviated with design and program maturation. Aleatory uncertainty is due to the inherent randomness of the system and cannot be directly reduced, unlike epistemic uncertainty. Robust design and probabilistic methods can compensate for aleatory effects. A taxonomy of uncertainty is referred to for this work [3]. In this paper, a probabilistic methodology to handle uncertainties has been demonstrated on a three-element HLS concept [1, 4], which allows tracking of current best estimates of the concept and assessment of concept design robustness against uncertainties. A sample case has been completed for this abstract, and an expansion on the methodology will be included in the final paper. This methodology has two key parts: first, the creation of a dynamic architecture model of a three-element HLS concept; and second, its use with surrogate modeling and range estimating techniques to capture and propagate uncertainties. This abstract will cover the basics of the approach used, and further details and justifications will be in the final paper.The mission profile associated with this three-element concept (Fig 1) was modeled as a set of mission events that facilitated mass changes, idles, or spacecraft maneuvers. The mission profile scope starts with each element’s NRHO orbit insertion and aggregation and ends at post-sortie rendezvous with Orion. More detail on the mission profile will be in the final paper. The DYnamic Rocket EQuation Tool (DYREQT), a space systems synthesis and sizing framework used by NASA, was used as the physics framework to model the HLS architecture for applying the probabilistic methodology [5, 6]. Specifically, a parametric representation of the lander, ascent, and transfer elements and the mission profile of each element was established, with vehicle and mission parameters available as inputs to allow for a dynamic model. Each vehicle stage was modeled with high-level performance metrics, using Isp and propellant mass fraction (PMF) to remain parametric. For the probabilistic analysis, uncertainties of interest within the HLS concept were enumerated and represented as parameters within the DYREQT model as inputs for vehicle stages or mission profile events. These parameters were frozen at their nominal values for the purposes of baselining architecture performance and sizing the vehicle appropriately based on reference documentation [1]. Range estimating—a probabilistic method that combines Monte Carlo sampling, focus on critical parameters, and heuristics to assess risk and opportunities—is traditionally used with Mass Equipment Lists (MELs), but has been adapted with operational parameters as well as vehicle parameters in theDYREQT model to capture mission uncertainty alongside vehicle uncertainty [7, 3]. This method was selected due to its application and insight on a system from a bottom-up perspective, independence from historical rules of thumb, and ability to generate sensitivities based on design decisions and uncertainties. As a sample case for the abstract, the boiloff rates of the vehicle elements and the loiter times during the mission (simulating launch time variations and changing window of opportunities) were used with range estimating to provide preliminary results. To perform the range estimation portion of this methodology (depicted in Fig. 3, further details in final paper), the DYREQT model was sampled using a Design of Experiments (DoE) to efficiently explore the architecture design space with respect to the sample set of uncertainty parameters; 5,000 cases via Latin Hypercube Sampling were computed on the DYREQT architecture model. Then, the results were used to create surrogate models, multivariate regressions that can visualize hypercube trends in the design space, of the architecture with respect to the uncertainty parameters. Range estimating was applied to the surrogates instead of the actual models, which saves computational expense due to the bulk of cases needed for the Monte Carlo simulation as part of range estimating. Uncertainty parameters were sampled independently from triangular distributions using the DoE ranges as ‘min’ and ‘max’, and the nominal value as ‘most likely’. Based engineering intuition, some uncertainty parameters are correlated—e.g. if the main propellant has a high boil-off rate, the oxidizer should follow suit as both are related to CFM technology.While a Monte Carlo simulation samples all inputs as independent, the results would show model correlations; thus, it is efficient to sample the inputs as correlated. Using a correlation matrix constructed for the uncertainty parameters, previously independent samples were transformed to perform a Correlated Monte Carlo. A table for the DoE ranges and probability distribution parameters is shown in Table 1, and more details on Correlated Monte Carlo Simulations will be discussed in the final paper. The model’s resulting DoE showed that multivariate polynomial equations fit via least squares method captured its behavior accurately for the sample case. For the Correlated Monte Carlo Simulation, a positive correlation between fuel and oxidizer boiloff rates was used as a demonstration. 10,000 cases were computed with the surrogates and the launched masses for each vehicle element was collated. The results can be displayed in a probability density function (PDF), showing the impact of the uncertainty parameters chosen. Integrating the PDFs will yield a cumulative distribution function (CDF) that shows the cumulative probability of a given value on the x-axis. For the sample case, the elements’ launch mass margin was calculated and represented in as CDFs, as a demonstrated representation of figures of merit for the HLS concept. For the lander and ascent elements, the NRHO mass insertion limit is 16t; the transfer element has a limit of 30t [1]. It can be seen with Figure 2 that this probabilistic methodology can provide insight into mass margin with respect to the uncertainties being modeled. Currently, the results show that the lander (descent) vehicle element has the most restrictive design space; it is the only element to show a 10% probability of negative margin. Further analysis on the Monte Carlo results will show sensitivities for driving constraints and parameters for architecture feasibility, which can lead to establishing potential mission rules.The combination of range estimating with a parametric architecture model for HLS demonstrated the capability of this probabilistic methodology in a sample case. As the HLS development progresses, this methodology has the potential for keeping current best estimates of architecture performance for awarded concepts due to the flexibility in DYREQT’s modeling framework and its parametric nature. Concept maturation and increased epistemic knowledge can be injected into the model probabilistic modeling, and thus continue to track probability of mission success.

Stephanie Y Zhu↗

Human cytochrome P450 17A1 structures with metabolites of prostate cancer drug abiraterone reveal substrate-binding plasticity and a second binding site

Abiraterone acetate is a first-line therapy for castration-resistant prostate cancer. This prodrug is deacetylated in vivo to abiraterone, which is a potent and specific inhibitor of cytochrome P450 17A1 (CYP17A1). CYP17A1 performs two sequential steps that are required for the biosynthesis of androgens that drive prostate cancer proliferation, analogous to estrogens in breast cancer. Abiraterone can be further metabolized in vivo on the steroid A ring to multiple metabolites that also inhibit CYP17A1. Despite its design as an active-site-directed substrate analog, abiraterone and its metabolites demonstrate mixed competitive/noncompetitive inhibition. To understand their binding, we solved the X-ray structures of CYP17A1 with three primary abiraterone metabolites. Despite different conformations of the steroid A ring and substituents, all three bound in the CYP17A1 active site with the steroid core packed against the I helix and the A ring C3 keto or hydroxyl oxygen forming a hydrogen bond with N202 similar to abiraterone itself. The structure of CYP17A1 with 3-keto, 5α-abiraterone was solved to 2.0 Å, the highest resolution to date for a CYP17A1 complex. This structure had additional electron density near the F/G loop, which is likely a second molecule of the inhibitor and which may explain the noncompetitive inhibition. Mutation of the adjacent Asn52 to Tyr positions its side chain in this space, maintains enzyme activity, and prevents binding of the peripheral ligand. Collectively, our findings provide further insight into abiraterone metabolite binding and CYP17A1 function.

59 BASIC BIOLOGICAL SCIENCES↗