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At least 1,333 records · Page 74

Model‐Based Approach to Selecting Pegfilgrastim Dose for Pharmacokinetic and Pharmacodynamic Similarity Studies in Biosimilar Development

This study applied modeling and simulation (M&S) approaches to evaluate the sensitivity of pegfilgrastim pharmacokinetics (PKs) and pharmacodynamics (PDs) to changes in dose amount, and linear or nonlinear clearance (CL) over pegfilgrastim subcutaneous dose of 2–6 mg. A previously published model was adapted to better describe pegfilgrastim PK and PD data in healthy subjects and used in simulation. Nonlinear CL accounts for 98% and 77%, respectively, of the total CL of pegfilgrastim at 2 and 6 mg. The sensitivity analyses showed: (i) PK of 2 and 6 mg doses are similarly sensitive to detect differences for a 5% change in dose; (ii) PK of 2 mg dose is more sensitive to changes in receptor binding affinity, a model parameter for nonlinear CL, and a product quality attribute characterized with orthogonal methods as part of demonstrating analytical similarity between products; (iii) PK of approved 6 mg dose is more sensitive to changes in linear CL, which has not been associated with any specific product quality attributes, and (iv) the PDs are not sensitive to changes in linear or nonlinear CL. Taken together, our analyses support that the approved pegfilgrastim dose of 6 mg is appropriate for detecting differences between a biosimilar and the reference products in pegfilgrastim PK and PD similarity studies. The described M&S approaches can be adopted to support dose selection for biosimilars with nonlinear PK and complex PK–PD interplay.

Pharmacology & Pharmacy↗

Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Development of 20 IEER Rooftop Units System Modeling and Building Energy Simulations

Based on detailed steady-state system and component modeling, we developed a rooftop unit system design, which is able to achieve IEER (Integrated Energy Efficiency Ratio) higher than 20. We modeled fin-&-tube and micro-channel heat exchangers using segment-to-segment approach, and use AHRI 10-coefficient compressor map to simulate compressor performance. The system modeling is based on a component-based modeling approach, which facilitates flexible simulation of complicated system configurations. Starting with a baseline system having IEER of 16.6, we extensively investigated numerous technical options, i.e. varying compressor sizes, heat exchanger fin densities, fin-&-tube or micro-channel heat exchanger, suction line heat exchanger, desiccant wheel, tandem compressor, variable-speed compressor, and condenser evaporative pre-cooling; and developed an innovative system configuration combining a tandem compression system with a variable-speed compression system. The combined system can achieve high IEER as well as process the outdoor ventilation air over an extensive range. We successfully evaluated the design concept for a 20-ton (70.4 kW) unit as well as a 10-ton (35.2 kW) unit. All the selected components are readily accessible on the market, and we validated the performance predictions against existing Rooftop Unit (RTU) products at the rating condition. This paper illustrates a potentially cost-effective high IEER RTU design. In addtion, we conducted extensive building energy simulations using EnergyPlus to predict seasonal energy saving potentials and peak power reductions using the High IEER RTU in sixteen US cities, in comparison to a RTU with a minimum efficiency.

Modeling↗

Modeling the Prodromal Effects and Performance Reduction of Astronauts from Exposure to Large Solar Particle Events

In space exploration outside the Earth's geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possibility of failure of the mission. Acute risks are especially of concern during spacewalks on the lunar surface because of the rapid onset of SPE's and science goals that involve long distances to crew habitats. Thus assessing the potential of early radiation effect under such adverse conditions is of prime importance. Here we present a biologic based mathematical model which describes the dose and time-dependent early human responses to ionizing radiation. We examine the possible early effects on crew behind various shielding materials from exposure to some historical large SPEs on the lunar and Mars surfaces. The doses and dose rates were calculated using the BRYNTRN code (Kim, M.Y, Hu, X, and Cucinotta, F.A, Effect of Shielding Materials from SPEs on the Lunar and Mars Surface, AIAA Space 2005, paper number AIAA-2005-6653, Long Beach, CA, August 30-September 1, 2005) and the hazard of the early radiation effects and performance reduction were calculated using the RIPD code (Anno, G.H, McClellan, G.E., Dore, M.A, Protracted Radiation-Induced Performance Decrement, Volume 1 Model Development,1996, Defense Nuclear Agency: Alexandria VA). Based on model assumptions we show that exposure to these historical SPEs do cause early effects to crew members and impair their performance if effective shielding and medical countermeasure tactics are not provided. The calculations show multiple occurrence of large SPEs in a short period of time significantly increase the severity of early illness, however early death from failure of the hematopoietic system is very unlikely because of the dose-rate and dose heterogeneity of SPEs. Results from these types of calculations will be a guide in design of protection systems and medical response strategy for astronauts in case of exposure to high dose irradiation during future space missions.

Hu, S.↗

Delivery of Dynamic Thermal Energy Storage Models and Advanced Reactor Concept Models to the HYBRID Repository

This publication details newly created energy storage and reactor models developed within the HYBRID modeling repository as part of the Department of Energy Office of Nuclear Energy (DOE-NE) Integrated Energy Systems (IES) program, led by Idaho National Laboratory (INL). Model development to-date includes creation of dynamic systems-level models of a pebble bed high temperature gas reactor (HTGR), sodium fast reactor (SFR), compressed air energy storage (CAES), liquid air energy storage (LAES) and Modelica standard library based two-tank sensible heat storage (SHS) in the IES-based HYBRID repository. Models are developed using the latest publicly available data and incorporate the possibility of control strategy inclusion for use with the existing IES modeling, analysis, and optimization toolset. Simulations showcase the abilities of each technology to flexibly operate in ways consistent with IES operation expectations. When these models are available, they can be utilized within different integrated energy park concepts to understand optimal system operation, control, and dispatching. Moreover, given the generic nature of the models, industrial partner technologies can be quickly added to the repository using the existing models as a basis. Additional dynamic models for thermal energy storage concepts can be developed and added to the HYBRID repository as needed. Also detailed in this report are future development goals for the HYBRID repository including adding suites of steady-state models, economic costing information, and reduced-order models. By adding these models in addition to the physical transient models currently existing within HYBRID, HYBRID will be a fully integrable tool for FORCE users.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Response of Silicon-Based Linear Energy Transfer Spectrometers: Implication for Radiation Risk Assessment in Space Flights

There is considerable interest in developing silicon-based telescopes because of their compactness and low power requirements. Three such telescopes have been flown on board the Space Shuttle to measure the linear energy transfer spectra of trapped, galactic cosmic ray, and solar energetic particles. Dosimeters based on single silicon detectors have also been flown on the Mir orbital station. A comparison of the absorbed dose and radiation quality factors calculated from these telescopes with that estimated from measurements made with a tissue equivalent proportional counter show differences which need to be fully understood if these telescopes are to be used for astronaut radiation risk assessments. Instrument performance is complicated by a variety of factors. A Monte Carlo-based technique was developed to model the behavior of both single element detectors in a proton beam, and the performance of a two-element, wide-angle telescope, in the trapped belt proton field inside the Space Shuttle. The technique is based on: (1) radiation transport intranuclear-evaporation model that takes into account the charge and angular distribution of target fragments, (2) Landau-Vavilov distribution of energy deposition allowing for electron escape, (3) true detector geometry of the telescope, (4) coincidence and discriminator settings, (5) spacecraft shielding geometry, and (6) the external space radiation environment, including albedo protons. The value of such detailed modeling and its implications in astronaut risk assessment is addressed. c2001 Elsevier Science B.V. All rights reserved.

manned↗

Model-Based Diagnostics for Propellant Loading Systems

The loading of spacecraft propellants is a complex, risky operation. Therefore, diagnostic solutions are necessary to quickly identify when a fault occurs, so that recovery actions can be taken or an abort procedure can be initiated. Model-based diagnosis solutions, established using an in-depth analysis and understanding of the underlying physical processes, offer the advanced capability to quickly detect and isolate faults, identify their severity, and predict their effects on system performance. We develop a physics-based model of a cryogenic propellant loading system, which describes the complex dynamics of liquid hydrogen filling from a storage tank to an external vehicle tank, as well as the influence of different faults on this process. The model takes into account the main physical processes such as highly nonequilibrium condensation and evaporation of the hydrogen vapor, pressurization, and also the dynamics of liquid hydrogen and vapor flows inside the system in the presence of helium gas. Since the model incorporates multiple faults in the system, it provides a suitable framework for model-based diagnostics and prognostics algorithms. Using this model, we analyze the effects of faults on the system, derive symbolic fault signatures for the purposes of fault isolation, and perform fault identification using a particle filter approach. We demonstrate the detection, isolation, and identification of a number of faults using simulation-based experiments.

Daigle, Matthew John↗

Microrheological modeling of lithium ion battery anode slurry

The rheological properties of electrode slurries used in the manufacturing of lithium-ion batteries affect the manufacturing processes as well as the battery quality, such as electrochemical and durability performance. There is thus an urgent need to develop a physics-based model to describe the rheological properties of these electrode slurries to enable further optimization of battery electrode production. Here in this paper, we present a microrheological model for estimating the viscosity of electrode slurries that incorporates colloidal forces such as van der Waals and polymeric steric repulsion forces. Finally, the model shows good agreement with the experimentally determined viscosities of a graphite-based anode slurry and should be extendable to describe the rheological properties of cathode slurries.

25 ENERGY STORAGE↗

Solar-Forecast GridAPPS-D Application [SWR-18-36]

Persistent model serves as the baseline in the intra-hour forecasting of solar radiation due to the extensive computing efforts from the numerical weather prediction (NWP) models and the lack of surface observations in cloud as well as other atmospheric properties. The smart persistent model actively updates the extraterrestrial solar radiation with time and is an important improvement from the persistent model while the cloud conditions are assumed unchanged by giving constant clear-sky indexes. We developed a Physics-based Smart Persistent model for Intra-hour solar forecasting (PSPI) to further improve the accuracy of the smart persistent model. We used a cloud retrieval technique developed by Xie and Liu (2013) to estimate cloudy fraction and cloud albedo using surface-based observations of solar radiation. The solar radiation in future time steps is accurately given by actively computing individual cloud albedo related to the future solar position. Our evaluation studies indicated that the PSPI model significantly increased the accuracy in the short-term forecast of solar radiation, especially in thin cloud conditions or those covered by broken clouds.

Xie, Yu↗

Dark Energy Survey Year 3 results: Simulation-based 𝑤CDM inference from weak lensing and galaxy clustering maps with deep learning: Analysis design

Data-driven approaches using deep learning are emerging as powerful techniques to extract non-Gaussian information from cosmological large-scale structure. Here, this work presents the first simulation-based inference (SBI) pipeline that combines weak lensing and galaxy clustering maps in a realistic Dark Energy Survey Year 3 (DES Y3) configuration and serves as preparation for a forthcoming analysis of the survey data. We develop a scalable forward model based on the CosmoGridV1 suite of N-body simulations to generate over one million self-consistent mock realizations of DES Y3 at the map level. Leveraging this large dataset, we train deep graph convolutional neural networks on the full survey footprint in spherical geometry to learn low-dimensional features that approximately maximize mutual information with target parameters. These learned compressions enable neural density estimation of the implicit likelihood via normalizing flows in a ten-dimensional parameter space spanning cosmological 𝑤CDM, intrinsic alignment, and linear galaxy bias parameters, while marginalizing over baryonic, photometric redshift, and shear bias nuisances. To ensure robustness, we extensively validate our inference pipeline using synthetic observations derived from both systematic contaminations in our forward model and independent Buzzard galaxy catalogs. Our forecasts yield significant improvements in cosmological parameter constraints, achieving 2−3× higher figures of merit in the 𝛺 𝑚 − 𝑆 8 plane relative to our implementation of baseline two-point statistics and effectively breaking parameter degeneracies through probe combination. These results demonstrate the potential of SBI analyses powered by deep learning for upcoming Stage-IV wide-field imaging surveys.

Thomsen, A. [Zurich, ETH] (ORCID:0000000203099021)↗

Mechanisms of crustal deformation in the western US

The deformation processes in the western United States were studied, considering both deterministic models and random or statistical models. The role of the intracrustal delamination and mechanisms of crustal thinning were also examined. The application of fractal techniques to understand how the crust is deforming was studied in complex regions. Work continued on the development of a fractal based model for deformation in the western United States. Fractal studies were also extended to the study of topography and the geoid.

Turcotte, Donald L.↗

Molecular-Based Optical Measurement Techniques for Transition and Turbulence in High-Speed Flow

High-speed laminar-to-turbulent transition and turbulence affect the control of flight vehicles, the heat transfer rate to a flight vehicle's surface, the material selected to protect such vehicles from high heating loads, the ultimate weight of a flight vehicle due to the presence of thermal protection systems, the efficiency of fuel-air mixing processes in high-speed combustion applications, etc. Gaining a fundamental understanding of the physical mechanisms involved in the transition process will lead to the development of predictive capabilities that can identify transition location and its impact on parameters like surface heating. Currently, there is no general theory that can completely describe the transition-to-turbulence process. However, transition research has led to the identification of the predominant pathways by which this process occurs. For a truly physics-based model of transition to be developed, the individual stages in the paths leading to the onset of fully turbulent flow must be well understood. This requires that each pathway be computationally modeled and experimentally characterized and validated. This may also lead to the discovery of new physical pathways. This document is intended to describe molecular based measurement techniques that have been developed, addressing the needs of the high-speed transition-to-turbulence and high-speed turbulence research fields. In particular, we focus on techniques that have either been used to study high speed transition and turbulence or techniques that show promise for studying these flows. This review is not exhaustive. In addition to the probe-based techniques described in the previous paragraph, several other classes of measurement techniques that are, or could be, used to study high speed transition and turbulence are excluded from this manuscript. For example, surface measurement techniques such as pressure and temperature paint, phosphor thermography, skin friction measurements and photogrammetry (for model attitude and deformation measurement) are excluded to limit the scope of this report. Other physical probes such as heat flux gauges, total temperature probes are also excluded. We further exclude measurement techniques that require particle seeding though particle based methods may still be useful in many high speed flow applications. This manuscript details some of the more widely used molecular-based measurement techniques for studying transition and turbulence: laser-induced fluorescence (LIF), Rayleigh and Raman Scattering and coherent anti-Stokes Raman scattering (CARS). These techniques are emphasized, in part, because of the prior experience of the authors. Additional molecular based techniques are described, albeit in less detail. Where possible, an effort is made to compare the relative advantages and disadvantages of the various measurement techniques, although these comparisons can be subjective views of the authors. Finally, the manuscript concludes by evaluating the different measurement techniques in view of the precision requirements described in this chapter. Additional requirements and considerations are discussed to assist with choosing an optical measurement technique for a given application.

Bathel, Brett F.↗

Towards operational atmospheric correction of airborne hyperspectral imaging spectroscopy: Algorithm evaluation, key parameter analysis, and machine learning emulators

Atmospheric correction of airborne hyperspectral imaging spectroscopy (AHIS) to obtain high-quality surface reflectance is the prerequisite for remote sensing applications. Over the last decades, different atmospheric correction methods have been developed based on radiative transfer models (RTMs), however, the relative performances of different algorithms are unclear. Automated operational atmospheric correction methods to process large-volume AHIS data in a high-accurate and high-throughput manner are still lacking. Therefore, this study proposed an operational atmospheric correction pipeline for deriving surface reflectance from AHIS data. To ensure the accuracy and efficiency of the pipeline, we focused on three specific aspects: (1) selecting a suitable RTM for the development of atmospheric lookup tables (LUTs) by comparing the commercial MODerate resolution atmospheric TRANsmission (MODTRAN) and open-sourced Library for Radiative TRANsfer (LibRadTRAN) models, where the widely-used software, Atmospheric/Topographic Correction for Airborne Imagery (ATCOR), was used as benchmarks; (2) identifying key atmospheric correction parameters and determining suitable sources for parameter retrievals including AHIS, Moderate Resolution Imaging Spectroradiometer (MODIS), and AErosol RObotic NETwork (AERONET); and (3) testing the performance of using machine learning emulators to speed up the RTM-based atmospheric correction. Results indicate that (1) atmospheric correction based on MODTRAN LUTs can produce surface reflectance accurately with mean absolute errors < 0.05 and cosine similarities > 0.98 compared to field measurements, which is comparable to the software ATCOR and slightly outperforms the LibRadTRAN LUTs; (2) sobol global sensitivity analysis demonstrates that in the atmospheric correction, visibility and water vapor are two key parameters that can be accurately derived from AHIS in contrast to MODIS or AERONET data; and (3) Random Forest emulators can produce accurate estimations of surface reflectance with mean absolute errors < 0.03 and cosine similarities > 0.98 for higher processing efficiency and determine a suitable set of wavelengths for retrieving atmospheric visibility and water vapor. In conclusion, the proposed atmospheric correction pipeline also improved the four-stream radiative transfer theory for airborne applications by considering adjacent effects from airborne surrounding pixels and can also be applied for atmospheric correction of hyperspectral data from spaceborne missions.

47 OTHER INSTRUMENTATION↗

Source Physics Experiment modeling: YEARLY REPORT FOR THE PERIOD Jan-Dec 2012

The Office of Nuclear Detonation Detection identifies characterization of the explosion source as a fundamental research area. Our ability to characterize explosion sources from earthquakes relies on empirical laws that are not covering all the possible cases of location, site structure and yields of possible explosions. Our empirical knowledge needs to be completed by a physical understanding of seismic wave generation. NA22 has funded the LANL SPE seismic project to develop a new source model under the Ground-Based Nuclear Explosion Monitoring Research and Development (GNEM-R&D) Program. NA22 also funds computational support of the seismic source model development. Hydrodynamic computations using realistic material response models combined with a comprehensive series of field experiments provided by the SPE program are needed for test and validation of the new seismic source models. The following three essential elements, (1) model development, (2) numerical simulations of non-linear material response, and (2) field experimentation, will be brought to bear on a predictive capability for broadband P and S wavefields with a sound physical basis for seismic monitoring applications. This research will advance our ability to address yield estimation for UNE conducted in proliferant nations and provide a better understanding of the coupling of explosion sources to the seismic wavefield.

58 GEOSCIENCES↗

Spacecraft Internal Acoustic Environment Modeling

The objective of the project is to develop an acoustic modeling capability, based on commercial off-the-shelf software, to be used as a tool for oversight of the future manned Constellation vehicles. The use of such a model will help ensure compliance with acoustic requirements. Also, this project includes modeling validation and development feedback via building physical mockups and conducting acoustic measurements to compare with the predictions.

Chu, S. Reynold↗

Multimegawatt dynamic NEP PMAD study

The National Aeronautics and Space Administration Lewis Research Center (NASA LeRC) is developing a FORTRAN-based model of a complete nuclear electric propulsion (NEP) vehicle to be used for piloted or cargo missions to the Moon or Mars. The proposed vehicle will use either a Brayton or K-Rankine power conversion cycle, and either ion or magnetoplasmadynamic (MPD) thrusters. In support of this effort, Rocketdyne evaluated various power management and distribution (PMAD) approaches and selected a low-frequency design that is based on the direct use of the alternator voltage and frequency for power transmission. This approach was compared with dc and high-frequency ac designs, and selected on the basis of mass, efficiency, and qualitative assessment of power quality, reliability and development costs. This low-frequency architecture will be used as the reference in future NEP PMAD studies and for the subsequent FORTRAN model development.

Metcalf, Kenneth J.↗

Measurement and modeling of muon-induced neutrons in LSM in application for direct dark matter searches

Due to a very low event rate expected in direct dark matter search experiments, a good understanding of every background component is crucial. Muon-induced neutrons constitute a prominent background, since neutrons lead to nuclear recoils and thus can mimic a potential dark matter signal. EDELWEISS is a Ge-bolometer experiment searching for WIMP dark matter. It is located in the Laboratoire Souterrain de Modane (LSM, France). We have measured muon-induced neutrons by means of a neutron counter based on Gd-loaded liquid scintillator. Studies of muon-induced neutrons are presented and include development of the appropriate MC model based on Geant4 and analysis of a 1000-days measurement campaign in LSM. We find a good agreement between measured rates of muon-induced neutrons and those predicted by the developed model with full event topology. The impact of the neutron background on current EDELWEISS data-taking as well as for next generation experiments such as EURECA is briefly discussed.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Modelling of fluorine based high density plasma for the etching of silica glasses

An etching simulator has been developed to study the etching of commercial silica glass (Pyrex, D263, AF45, and Vycor) in a SF{sub 6}/Ar inductively coupled plasma (ICP) discharge. The etching model is based on the development of the plasma kinetic model coupled to a two dimensional (2D) Monte Carlo cellular surface model to predict the etched surface morphology as a function of the operating conditions. The SF{sub 6}/Ar plasma model allows us to predict the neutral and ion species fluxes, as well as the density and the temperature of electrons, as a function of the reactor operating conditions. Such output parameters are used as input parameters in both the sheath and etching models. The 2D Monte Carlo cellular model is based on the representation of both the substrate and the mask by uniform cells, which each represents a real number of sites. The preferential redeposition mechanism of the etched products on the metallic sites seems to play an important role on the formation and the propagation of the etched surface roughness. The results obtained by the model are compared with the experimental results for etching rate and roughness. A satisfactory agreement between the experimental results and the model concerning the etching rate and the etched surface morphology has been obtained for different glasses.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗