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DOE OSTI2016

Advanced Methods for Modeling Water-Levels and Estimating Drawdowns with SeriesSEE, an Excel Add-In

Water-level modeling is used for multiple-well aquifer tests to reliably differentiate pumping responses from natural water-level changes in wells, or environmental fluctuations. Synthetic water levels are created during water-level modeling and represent the summation of multiple component fluctuations, including those caused by environmental forcing and pumping. Pumping signals are modeled by transforming step-wise pumping records into water-level changes by using superimposed Theis functions. Water-levels can be modeled robustly with this Theis-transform approach because environmental fluctuations and pumping signals are simulated simultaneously. Water-level modeling with Theis transforms has been implemented in the program SeriesSEE, which is a Microsoft® Excel add-in. Moving average, Theis, pneumatic-lag, and gamma functions transform time series of measured values into water-level model components in SeriesSEE. Earth tides and step transforms are additional computed water-level model components. Water-level models are calibrated by minimizing a sum-of-squares objective function where singular value decomposition and Tikhonov regularization stabilize results. Drawdown estimates from a water-level model are the summation of all Theis transforms minus residual differences between synthetic and measured water levels. The accuracy of drawdown estimates is limited primarily by noise in the data sets, not the Theis-transform approach. Drawdowns much smaller than environmental fluctuations have been detected across major fault structures, at distances of more than 1 mile from the pumping well, and with limited pre-pumping and recovery data at sites across the United States. In addition to water-level modeling, utilities exist in SeriesSEE for viewing, cleaning, manipulating, and analyzing time-series data.

58 GEOSCIENCES↗

DOE OSTI2016

ACCURATE MODELING OF X-RAY EXTINCTION BY INTERSTELLAR GRAINS

Interstellar abundance determinations from fits to X-ray absorption edges often rely on the incorrect assumption that scattering is insignificant and can be ignored. We show instead that scattering contributes significantly to the attenuation of X-rays for realistic dust grain size distributions and substantially modifies the spectrum near absorption edges of elements present in grains. The dust attenuation modules used in major X-ray spectral fitting programs do not take this into account. We show that the consequences of neglecting scattering on the determination of interstellar elemental abundances are modest; however, scattering (along with uncertainties in the grain size distribution) must be taken into account when near-edge extinction fine structure is used to infer dust mineralogy. We advertise the benefits and accuracy of anomalous diffraction theory for both X-ray halo analysis and near edge absorption studies. We present an open source Fortran suite, General Geometry Anomalous Diffraction Theory (GGADT), that calculates X-ray absorption, scattering, and differential scattering cross sections for grains of arbitrary geometry and composition.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2022

Simulation of CEFR neutronic start-up tests with FENNECS

This paper presents simulation results of selected Neutronic Start-up Tests of the China Experimental Fast Reactor (CEFR) obtained by the neutronics code FENNECS that have been performed within the frame of the IAEA Coordinated Research Program I31032. The Finite Element Neutronics code FENNECS is developed at GRS and solves the few-group steady-state and transient diffusion equation using a Galerkin-based finite element approach. Its main purpose is the safety assessment of Small Modular Reactors and Micro Reactors with complex geometry (e.g., rotating control drums) which gain increased interest internationally. Serpent has been applied to create reference models of the CEFR and cross-section libraries in 10 energy groups for FENNECS. Using these libraries, the following experiments have been simulated with FENNECS: net criticality, control rod integral and differential worth, void reactivity effect, subassembly exchange reactivity effects and reaction rate distribution. The obtained satisfactory agreements with the measurements represent a valuable contribution to the validation of FENNECS. (author)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2014

Communication: Localized molecular orbital analysis of the effect of electron correlation on the anomalous isotope effect in the NMR spin-spin coupling constant in methane

We discuss the effect of electron correlation on the unexpected differential sensitivity (UDS) in the {sup 1}J(C–H) coupling constant of CH{sub 4} using a decomposition into contributions from localized molecular orbitals and compare with the {sup 1}J(N–H) coupling constant in NH{sub 3}. In particular, we discuss the well known fact that uncorrelated coupled Hartree-Fock (CHF) calculations are not able to reproduce the UDS in methane. For this purpose we have implemented for the first time a localized molecular orbital analysis for the second order polarization propagator approximation with coupled cluster singles and doubles amplitudes—SOPPA(CCSD) in the DALTON program. Comparing the changes in the localized orbital contributions at the correlated SOPPA and SOPPA(CCSD) levels and at the uncorrelated CHF level, we find that the latter overestimates the effect of stretching the bond between the coupled atoms on the contribution to the coupling from the localized bonding orbital between these atoms. This disturbs the subtle balance between the molecular orbital contributions, which lead to the UDS in methane.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2025

The Functor system: a new on-the-fly take on Material Properties based on C++ functions

In the context of solving multiphysics problems, the discretization of the partial differential equations (PDE) at hand often takes the spotlight. However, for most engineering users and even application developers, the discretization of the equations has already been performed. Instead, they are tasked with implementing specific closure relations and material properties. MOOSE has long enabled this using the Materials system. This system relied on the pre-computation of all properties before they are used in the PDE or in postprocessing. In this talk we will introduce the Functor system, which was deployed in MOOSE in 2021, then present a few applications of functors in flow modeling simulations by the NEAMS program. Functors first offer great flexibility in their evaluation. Rather than storing various arrays for material properties, they are evaluated on the fly at the location and state, e.g. current or old value, requested. Unlike regular material properties, several operations such as the time derivative, the divergence and the curl can be requested from a functor. Similar to material properties, functors can be made to depend on arbitrary combinations of variables, functions, postprocessors and other properties. However, unlike material properties, any of these can be substituted for a functor material property. Thanks to this, objects no longer need to be duplicated based on the types of their parameters.

97 - MATHEMATICS AND COMPUTING↗

DOE OSTI2015

A User Guide to PARET/ANL (V.7.6) (Rev.1)

PARET was originally created in 1969 at what is now Idaho National Laboratory (INL), to analyze reactivity insertion events in research and test reactor cores cooled by light or heavy water, with fuel composed of either plates or pins. The use of PARET is also appropriate for fuel assemblies with curved fuel plates when their radii of curvatures are large with respect to the fuel plate thickness. The PARET/ANL version of the code has been developed at Argonne National Laboratory (ANL) under the sponsorship of the U.S. Department of Energy/NNSA, and has been used by the Reactor Conversion Program to determine the expected transient behavior of a large number of reactors. PARET/ANL models the various fueled regions of a reactor core as channels. Each of these channels consists of a single flat fuel plate/pin (including cladding and, optionally, a gap) with water coolant on each side. In slab geometry the coolant channels for a given fuel plate are of identical dimensions (mirror symmetry), but they can be of different thickness in each channel. There can be many channels, but each channel is independent and coupled only through reactivity feedback effects to the whole core. The time-dependent differential equations that represent the system are replaced by an equivalent set of finite-difference equations in space and time, which are integrated numerically. PARET/ANL uses fundamentally the same numerical scheme as RELAP5 for the time-integration of the point-kinetics equations. The one-dimensional thermal-hydraulic model includes temperature-dependent thermal properties of the solid materials, such as heat capacity and thermal conductivity, as well as the transient heat production and heat transfer from the fuel meat to the coolant. Temperature- and pressure-dependent thermal properties of the coolant such as enthalpy, density, thermal conductivity, and viscosity are also used in determining parameters such as friction factors and heat transfer coefficients. The code first determines the steady-state solution for the initial state. Then the solution of the transient is obtained by integration in time and space. Multiple heat transfer, DNB and flow instability correlations are available. The code was originally developed to model reactors cooled by an open loop, which was adequate for rapid transients in pool-type cores. An external loop model appropriate for Miniature Neutron Source Reactors (MNSR’s) was also added to PARET/ANL to model natural circulation within the vessel, heat transfer from the vessel to pool and heat loss by evaporation from the pool. PARET/ANL also contains models for decay heat after shutdown, control rod reactivity versus time or position, time-dependent pump flow, and loss-of-flow event with flow reversal as well as logic for trips on period, power, and flow. Feedback reactivity effects from coolant density changes and temperature changes are represented by tables. Feedback reactivity from fuel heat-up (Doppler Effect) is represented by a four-term polynomial in powers of fuel temperature. Photo-neutrons produced in beryllium or in heavy water may be included in the point-kinetics equations by using additional delayed neutron groups.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2019

A User Guide to PARET/ANL

PARET was originally created in 1969 at what is now Idaho National Laboratory (INL), to analyze reactivity insertion events in research and test reactor cores cooled by light or heavy water, with fuel composed of either plates or pins. The use of PARET is also appropriate for fuel assemblies with curved fuel plates when their radii of curvatures are large with respect to the fuel plate thickness. The PARET/ANL version of the code has been developed at Argonne National Laboratory (ANL) under the sponsorship of the U.S. Department of Energy/NNSA since the inception of the Reactor Conversion Program. Since Reduced Enrichment for Research and Test Reactors (RERTR) began in 1978, PARET/ANL has been benchmarked to experimental data including SPERT testing, and used to determine the expected transient behavior of a large number of reactors regardless of enrichment both inside and outside the Reactor Conversion Program. This document provides the pertinent information for the use of PARET/ANL Version 7.6. PARET/ANL models the various fueled regions of a reactor core as channels. Each of these channels consists of a single flat fuel plate/pin (including cladding and, optionally, a gap) with water coolant on each side. In slab geometry the coolant channels for a given fuel plate are of identical dimensions (mirror symmetry), but they can be of different thickness in each channel. There can be many channels, but each channel is independent and coupled only through reactivity feedback effects to the whole core. The time-dependent differential equations that represent the system are replaced by an equivalent set of finite-difference equations in space and time, which are integrated numerically. PARET/ANL uses fundamentally the same numerical scheme as RELAP5 for the time-integration of the point-kinetics equations. The one-dimensional thermal-hydraulic model includes temperature-dependent thermal properties of the solid materials, such as heat capacity and thermal conductivity, as well as the transient heat production and heat transfer from the fuel meat to the coolant. Temperature- and pressure-dependent thermal properties of the coolant such as enthalpy, density, thermal conductivity, and viscosity are also used in determining parameters such as friction factors and heat transfer coefficients. The code first determines the steady-state solution for the initial state. Then the solution of the transient is obtained by integration in time and space. Multiple heat transfer, DNB and flow instability correlations are available. The code was originally developed to model reactors cooled by an open loop, which was adequate for rapid transients in pool-type cores. An external loop model appropriate for Miniature Neutron Source Reactors (MNSR’s) was also added to PARET/ANL to model natural circulation within the vessel, heat transfer from the vessel to pool and heat loss by evaporation from the pool. PARET/ANL also contains models for decay heat after shutdown, control rod reactivity versus time or position, time-dependent pump flow, and loss-of-flow event with flow reversal as well as logic for trips on period, power, and flow. Feedback reactivity effects from coolant density changes and temperature changes are represented by tables. Feedback reactivity from fuel heat-up (Doppler Effect) is represented by a four-term polynomial in powers of fuel temperature. Photo-neutrons produced in beryllium or in heavy water may be included in the point-kinetics equations by using additional delayed neutron groups.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2022

A User Guide to PARET/ANL

PARET was originally created in 1969 at what is now Idaho National Laboratory (INL), to analyze reactivity insertion events in research and test reactor cores cooled by light or heavy water, with fuel composed of either plates or pins. The use of PARET is also appropriate for fuel assemblies with curved fuel plates when their radii of curvatures are large with respect to the fuel plate thickness. The PARET/ANL version of the code has been developed at Argonne National Laboratory (ANL) under the sponsorship of the U.S. Department of Energy/NNSA since the inception of the Reactor Conversion Program. Since Reduced Enrichment for Research and Test Reactors (RERTR) began in 1978, PARET/ANL has been benchmarked to experimental data including SPERT testing, and used to determine the expected transient behavior of a large number of reactors regardless of enrichment both inside and outside the Reactor Conversion Program. This document provides the pertinent information for the use of PARET/ANL Version 7.6. PARET/ANL models the various fueled regions of a reactor core as channels. Each of these channels consists of a single flat fuel plate/pin (including cladding and, optionally, a gap) with water coolant on each side. In slab geometry the coolant channels for a given fuel plate are of identical dimensions (mirror symmetry), but they can be of different thickness in each channel. There can be many channels, but each channel is independent and coupled only through reactivity feedback effects to the whole core. The time-dependent differential equations that represent the system are replaced by an equivalent set of finite-difference equations in space and time, which are integrated numerically. PARET/ANL uses fundamentally the same numerical scheme as RELAP5 for the time-integration of the point-kinetics equations. The one-dimensional thermal-hydraulic model includes temperature-dependent thermal properties of the solid materials, such as heat capacity and thermal conductivity, as well as the transient heat production and heat transfer from the fuel meat to the coolant. Temperature- and pressure-dependent thermal properties of the coolant such as enthalpy, density, thermal conductivity, and viscosity are also used in determining parameters such as friction factors and heat transfer coefficients. The code first determines the steady-state solution for the initial state. Then the solution of the transient is obtained by integration in time and space. Multiple heat transfer, DNB and flow instability correlations are available. The code was originally developed to model reactors cooled by an open loop, which was adequate for rapid transients in pool-type cores. An external loop model appropriate for Miniature Neutron Source Reactors (MNSR’s) was also added to PARET/ANL to model natural circulation within the vessel, heat transfer from the vessel to pool and heat loss by evaporation from the pool. PARET/ANL also contains models for decay heat after shutdown, control rod reactivity versus time or position, time-dependent pump flow, and loss-of-flow event with flow reversal as well as logic for trips on period, power, and flow. Feedback reactivity effects from coolant density changes and temperature changes are represented by tables. Feedback reactivity from fuel heat-up (Doppler Effect) is represented by a four-term polynomial in powers of fuel temperature. Photo-neutrons produced in beryllium or in heavy water may be included in the point-kinetics equations by using additional delayed neutron groups.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2017

Precision Measurement of the Eta Radiative Decay Width via the Primakoff Effect with GlueX

The GlueX detector in the experimental Hall-D at Jefferson Lab provides a unique capability to perform a measurement of the eta to gamma gamma decay width via the Primakoff effect with the precision significantly better than all existing collider and Primakoff results. The experiment will measure differential cross sections of eta mesons at forward angles on a liquid hydrogen and helium targets using a beam of tagged photons, which will be used for the extraction of the decay width. The measurement is essential for the determination of the fundamental properties such as the ratios of the light quark masses and the eta eta-prime mixing angle, and will provide an important test of chiral symmetry breaking in QCD. The experimental results will also allow to significantly reduce uncertainties on partial widths of all other eta decays. We will give an overview the PrimEx-D physics program and experimental setup.

Somov, Alexander↗

DOE OSTI2016

Exclusive single pion electroproduction off the proton: Results from CLAS

Exclusive meson electroproduction off protons is a powerful tool to probe the effective degrees of freedom in excited nucleon states at the varying distance scale where the transition from the contributions of both quark core and meson-baryon cloud to the quark core dominance. During the past decade, the CLAS collaboration has executed a broad experimental program to study the excited states of the proton using polarized electron beam and both polarized and unpolarized proton targets. The measurements covered a broad kinematic range in the invariant mass $W$ and photon virtuality $Q^2$ with nearly full coverage in polar and azimuthal angles in the hadronic CM system. As results, several low-lying nucleon resonance states in particular from pion threshold to $W < 1.6$ GeV have been explored. These include $\Delta$(1232)$\frac{3}{2}^+$, $N(1440)\frac{1}{2}^+$, $N(1520)\frac{3}{2}^-$, and $N(1535)\frac{1}{2}^-$ states. In addition, we recently published the differential cross sections and helicity amplitudes of the reaction $\gamma^*p\to n\pi^+$ at higher $W$ (1.6 to 2.0 GeV) which are the $N(1675)\frac{5}{2}^-$, $N(1680)\frac{5}{2}^+$, and $N(1710)\frac{1}{2}^+$ states. These excited states with isospin $1/2$ and with masses near 1.7 GeV can be accessed in single $n\pi^+$ production as there are no isospin $3/2$ states present in this mass range with the same spin-parity assignments. As a result, I will briefly discuss these states from CLAS results of the single charged pion electroproduction data.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

DOE OSTI2018

Fast Approximate Union Volume in High Dimensions with Line Samples

The classical problem of calculating the volume of the union of d-dimensional balls is known as "Union Volume." We present line-sampling approximation algorithms for Union Volume. Our methods may be extended to other Boolean operations, such as setminus; or to other shapes, such as hyper-rectangles. The deterministic, exact approaches for Union Volume do not scale well to high dimensions. However, we adapt several of these exact approaches to approximation algorithms based on sampling. We perform local sampling within each ball using lines. We have several variations, depending on how the overlapping volume is partitioned, and depending on whether radial, axis-aligned, or other line patterns are used. Our variations fall within the family of Monte Carlo sampling, and hence have about the same theoretical convergence rate, 1 /$\sqrt{M}$, where M is the number of samples. In our limited experiments, line-sampling proved more accurate per unit work than point samples, because a line sample provides more information, and the analytic equation for a sphere makes the calculation almost as fast. We performed a limited empirical study of the efficiency of these variations. We suggest a more extensive study for future work. We speculate that different ball arrangements, differentiated by the distribution of overlaps in terms of volume and degree, will benefit the most from patterns of line samples that preferentially capture those overlaps. Acknowledgement We thank Karl Bringman for explaining his BF-ApproxUnion (ApproxUnion) algorithm [3] to us. We thank Josiah Manson for pointing out that spoke darts oversample the center and we might get a better answer by uniform sampling. We thank Vijay Natarajan for suggesting random chord sampling. The authors are grateful to Brian Adams, Keith Dalbey, and Vicente Romero for useful technical discussions. This work was sponsored by the Laboratory Directed Research and Development (LDRD) Program at Sandia National Laboratories. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Advanced Scientific Computing Research (ASCR), Applied Mathematics Program. Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2015

Exclusive Single Pion off the Proton: Results from CLAS

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

DOE OSTI2026

February DOE Office of Science Highlight Slides

Highlight slides for submission to DOE Office of Science program managers.

37 - INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL C↗

DOE OSTI2019

Juxtatumoral perinephric fat analysis in clear cell renal cell carcinoma

Purpose: The purpose of the study was to evaluate the feasibility of using contrast-enhanced computed tomography (CECT)-based texture analysis (CTTA) metrics to differentiate between juxtatumoral perinephric fat (JPF) surrounding low-grade (ISUP 1–2) versus high-grade (ISUP 3–4) clear cell renal cell carcinoma (ccRCC). Methods: In this IRB-approved study, we retrospectively queried the surgical database between June 2009 and April 2016 and identified 83 patients with pathologically confirmed ccRCC (low grade: n = 54, mean age = 61.5 years, 18F/35M; high grade n = 30, mean age = 61.7 years, 8F/22M) who also had pre-operative multiphase CT acquisitions. CT images were transferred to a 3D workstation, and nephrographic phase JPF regions were manually segmented. Using an in-house developed Matlab program, a CTTA panel comprising of texture metrics extracted using six different methods, histogram, 2D- and 3D-Gray-level co-occurrence matrix (GLCM) and Gray-level difference matrix (GLDM), and 2D-Fast Fourier Transform (FFT) analyses, was applied to the segmented images to assess JPF textural heterogeneity in low- versus high-grade ccRCC. Univariate analysis and receiver-operator characteristics (ROC) analysis were used to assess interclass differences in texture metrics and their prediction accuracy, respectively. Results: All methods except GLCM consistently revealed increased heterogeneity in the JPF surrounding high- versus low-grade ccRCC. FFT showed increased complexity index (p < 0.01). Histogram analysis showed increased kurtosis and positive skewness in (p < 0.03), and GLDM analysis showed decreased measure of correlation coefficient (MCC) (p < 0.04). Several of the GLCM metrics showed statistically significant (p < 0.04) textural differences between the two groups, but with no consistent trend. ROC analysis showed that MCC in GLCM analysis had an area under the curve of 0.75. Conclusions: Our study suggests that CTTA of ccRCC shows statistically significant textural differences in JPF surrounding high- versus low-grade ccRCC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2012

Pre-Combustion Carbon Capture by a Nanoporous, Superhydrophobic Membrane Contactor Process

This report summarizes progress made during Phase I and Phase II of the project: "Pre-Combustion Carbon Capture by a Nanoporous, Superhydrophobic Membrane Contactor Process," under contract DE-FE-0000646. The objective of this project is to develop a practical and cost effective technology for CO 2 separation and capture for pre-combustion coal-based gasification plants using a membrane contactor/solvent absorption process. The goals of this technology development project are to separate and capture at least 90% of the CO 2 from Integrated Gasification Combined Cycle (IGCC) power plants with less than 10% increase in the cost of energy services. Unlike conventional gas separation membranes, the membrane contactor is a novel gas separation process based on the gas/liquid membrane concept. The membrane contactor is an advanced mass transfer device that operates with liquid on one side of the membrane and gas on the other. The membrane contactor can operate with pressures that are almost the same on both sides of the membrane, whereas the gas separation membranes use the differential pressure across the membrane as driving force for separation. The driving force for separation for the membrane contactor process is the chemical potential difference of CO 2 in the gas phase and in the absorption liquid. This process is thus easily tailored to suit the needs for pre-combustion separation and capture of CO 2 . Gas Technology Institute (GTI) and PoroGen Corporation (PGC) have developed a novel hollow fiber membrane technology that is based on chemically and thermally resistant commercial engineered polymer poly(ether ether ketone) or PEEK. The PEEK membrane material used in the membrane contactor during this technology development program is a high temperature engineered plastic that is virtually non-destructible under the operating conditions encountered in typical gas absorption applications. It can withstand contact with most of the common treating solvents. GTI and PGC have developed a nanoporous and superhydrophobic PEEK-based hollow fiber membrane contactor tailored for the membrane contactor/solvent absorption application for syngas cleanup. The membrane contactor modules were scaled up to 8-inch diameter commercial size modules. We have performing extensive laboratory and bench testing using pure gases, simulated water-gas-shifted (WGS) syngas stream, and a slipstream from a gasification derived syngas from GTI's Flex-Fuel Test Facility (FFTF) gasification plant under commercially relevant conditions. The team have also carried out an engineering and economic analysis of the membrane contactor process to evaluate the economics of this technology and its commercial potential. Our test results have shown that 90% CO 2 capture can be achieved with several physical solvents such as water and chilled methanol. The rate of CO 2 removal by the membrane contactor is in the range of 1.5 to 2.0 kg/m 2 /hr depending on the operating pressures and temperatures and depending on the solvents used. The final economic analysis has shown that the membrane contactor process will cause the cost of electricity to increase by 21% from the base plant without CO 2 capture. The goal of 10% increase in levelized cost of electricity (LCOE) from base DOE Case 1(base plant without capture) is not achieved by using the membrane contactor. However, the 21% increase in LCOE is a substantial improvement as compared with the 31.6% increase in LCOE as in DOE Case 2(state of art capture technology using 2-stages of Selexol TM ).

01 COAL, LIGNITE, AND PEAT↗

DOE OSTI2019

A memory-distributed quasi-Newton solver for nonlinear programming problems with a small number of general constraints

We approach the problem of parallelizing state-of-the-art nonlinear programming optimization algorithms.Specifically, we focus on parallelizing quasi-Newton interior-point methods that use limited-memory secant Hessian approximations. Such interior-point methods are known to have better convergence properties and to be more effective on large-scale problems than gradient-based and derivative-free optimization algorithms. We target nonlinear and potentially nonconvex optimization problems with an arbitrary number of bound constraints and a small number of general equality and inequality constraints on the optimization variables. These problems occur for example in the form of optimal control, optimal design, and inverse problems governed by ordinary or partial differential equations, whenever they are expressed in a “reduced-space” optimization approach. We introduce and analyze the time and space complexity of a decomposition method for solving the quasi-Newton linear systems that leverages the fact that the quasi-Newton Hessian matrix has a small number of dense blocks that border a low-rank update of a diagonal matrix. This enables an efficient parallelization on memory-distributed computers of the iterations of the optimization algorithm, a state-of-the-art filter line-search interior-point algorithm by Wächter et. al. We illustrate the efficiency of the proposed method by solving structural topology optimization problems on up to 4608 cores on a parallel machine.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2011

Global Gene Expression Analysis of Murine Limb Development

Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ,30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

IL-10 Signaling Elicited by Nivolumab-Induced Activation of the $\mathrm{MAP}$ Kinase Pathway Does Not Fully Contribute to Nivolumab-Modulated Heterogeneous T Cell Responses

Immune checkpoint inhibitor (ICI) therapy has revolutionized anti-cancer treatment for many late-stage cancer patients. However, ICI therapy has thus far demonstrated limited efficacy for most patients, and it remains unclear why this is so. Interleukin 10 (IL-10) is a cytokine that has been recognized as a central player in cancer biology with its ability to inhibit anti-tumor T cell responses. Recent studies suggest that IL-10 might also exert some intrinsic anti-tumor T cell responses, and clinical studies using recombinant IL-10 alone or in combination with ICI are underway. This paradoxical effect of IL-10 and its underlying mechanisms impacting ICI-modulated T cell responses remain poorly understood. In this study, using an in vitro mixed lymphocyte reaction assay, we found that treatment with ICIs such as the anti-programmed cell death receptor-1 (PD-1) mAb nivolumab elicits a strong expression of IL-10. While neutralization of IL-10 signaling with an anti-IL-10 specific mAb significantly decreases the production of IFN-γ by T cells in a cohort of donor cells, the opposite effect was observed in other donor cells. Similarly, neutralization of IL-10 signaling significantly decreases the expression of T cell activation markers Ki67 and CD25, as well as the production of Granzyme B in a cohort of donor cells, whereas the opposite effect was observed in others. Furthermore, we found that nivolumab and IL-10 differentially modulate the signal transducer and activator of transcription 3 (STAT3) and AKT serine–threonine kinase pathways. Finally, we found that nivolumab activates the mitogen-activated protein kinase (MAPK) pathway, which in turn is responsible for the observed induction of IL-10 production by nivolumab. These findings provide new insights into the mechanisms underlying anti-PD-1-modulated T cell responses by IL-10, which could lead to the discovery of novel combination treatments that target IL-10 and immune checkpoint molecules.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗