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

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

The four-loop six-gluon NMHV ratio function

We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar N=4 super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a Q¯ differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We test the result against multi-Regge predictions at NNLL and N 3 LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We study the analytical and numerical behavior of the parity-even and parity-odd parts on various lines and surfaces traversing the three-dimensional space of cross ratios. As part of this program, we characterize all irreducible hexagon functions through weight eight in terms of their coproduct. As a result, we also provide representations of the ratio function in particular kinematic regions in terms of multiple polylogarithms.

1/N expansion↗
DOE OSTI2022

Simultaneous Observations of Surface Layer Profiles of Humidity, Temperature, and Wind Using Scanning Lidar Instruments

We demonstrate the combination of three Doppler lidars (DLs), a water vapor differential absorption lidar and a temperature rotational Raman lidar for the investigation of the interactions between the land-surface and the atmospheric boundary layer. This combination of scanning lidars was operated for the first time during the Land-Atmosphere Feedback Experiment at the Atmospheric Radiation Measurement program's Southern Great Plain site, Oklahoma, USA, in August 2017, and provided simultaneous surface layer profiles of horizontal wind, humidity and temperature. The horizontal wind profiles were determined using the dual-Doppler method with two DLs. The scans were performed above four towers providing atmospheric variables and fluxes. These combined lidar data allowed for the estimation of the friction velocity as well as the surface latent and sensible heat fluxes. For this purpose, profiles calculated with Monin-Obukhov similarity theory were fitted with the Levenberg-Marquardt nonlinear least squares curve-fitting method to the measured surface-layer lidar profiles. We present case studies of three 50-min periods to illustrate the new method. The measurements resulted in friction velocities of 0.31, 0.29, and 0.38 ms –1 , sensible surface heat fluxes of 312.1, 234.1, and 183.3 Wm –2 and latent surface heat fluxes of 251.8, 227.3, and 274.4 Wm –2 . These values were compared with the in-situ measurements of the towers. Considering the sampling differences and the error analyses, the results agree within 25.1%, 42.5%, and 28.8%, respectively, demonstrating that this synergy of scanning active remote sensing systems can be used to derive surface fluxes with reasonable accuracy.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Mathematical solutions in internal dose assessment: A comparison of Python-based differential equation solvers in biokinetic modeling

Abstract In biokinetic modeling systems employed for radiation protection, biological retention and excretion have been modeled as a series of discretized compartments representing the organs and tissues of the human body. Fractional retention and excretion in these organ and tissue systems have been mathematically governed by a series of coupled first-order ordinary differential equations (ODEs). The coupled ODE systems comprising the biokinetic models are usually stiff due to the severe difference between rapid and slow transfers between compartments. In this study, the capabilities of solving a complex coupled system of ODEs for biokinetic modeling were evaluated by comparing different Python programming language solvers and solving methods with the motivation of establishing a framework that enables multi-level analysis. The stability of the solvers was analyzed to select the best performers for solving the biokinetic problems. A Python-based linear algebraic method was also explored to examine how the numerical methods deviated from an analytical or semi-analytical method. Results demonstrated that customized implicit methods resulted in an enhanced stable solution for the inhaled 60 Co (Type M) and 131 I (Type F) exposure scenarios for the inhalation pathway of the International Commission on Radiological Protection (ICRP) Publication 130 Human Respiratory Tract Model (HRTM). The customized implementation of the Python-based implicit solvers resulted in approximately consistent solutions with the Python-based matrix exponential method ( expm ). The differences generally observed between the implicit solvers and expm are attributable to numerical precision and the order of numerical approximation of the numerical solvers. This study provides the first analysis of a list of Python ODE solvers and methods by comparing their usage for solving biokinetic models using the ICRP Publication 130 HRTM and provides a framework for the selection of the most appropriate ODE solvers and methods in Python language to implement for modeling the distribution of internal radioactivity.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2015

MANTA. An Integral Reactor Physics Experiment to Infer the Neutron Capture Cross Sections of Actinides and Fission Products in Fast and Epithermal Spectra

Neutron cross-sections characterize the way neutrons interact with matter. They are essential to most nuclear engineering projects and, even though theoretical progress has been made as far as the predictability of neutron cross-section models, measurements are still indispensable to meet tight design requirements for reduced uncertainties. Within the field of fission reactor technology, one can identify the following specializations that rely on the availability of accurate neutron cross-sections: (1) fission reactor design, (2) nuclear fuel cycles, (3) nuclear safety, (4) nuclear safeguards, (5) reactor monitoring and neutron fluence determination and (6) waste disposal and transmutation. In particular, the assessment of advanced fuel cycles requires an extensive knowledge of transuranics cross sections. Plutonium isotopes, but also americium, curium and up to californium isotope data are required with a small uncertainty in order to optimize significant features of the fuel cycle that have an impact on feasibility studies (e.g. neutron doses at fuel fabrication, decay heat in a repository, etc.). Different techniques are available to determine neutron cross sections experimentally, with the common denominator that a source of neutrons is necessary. It can either come from an accelerator that produces neutrons as a result of interactions between charged particles and a target, or it can come from a nuclear reactor. When the measurements are performed with an accelerator, they are referred to as differential since the analysis of the data provides the cross-sections for different discrete energies, i.e. σ(E i ), and for the diffusion cross sections for different discrete angles. Another approach is to irradiate a very pure sample in a test reactor such as the Advanced Test Reactor (ATR) at INL and, after a given time, determine the amount of the different transmutation products. The precise characterization of the nuclide densities before and after neutron irradiation allows to infer energy-integrated neutron cross sections, i.e. ∫₀ ∞ σ(E)φ(E)dE, where φ(E) is the neutron flux “seen” by the sample. This approach, which is usually defined and led by reactor physicists, is referred to as integral and is the object of this report. These two sources of information, i.e. differential and integral, are complementary and are used by the nuclear physicists in charge of producing the evaluated nuclear data files used by the nuclear community (ENDF, JEFF…). The generation of accurate nuclear data files requires an iterative process involving reactor physicists and nuclear data evaluators. This experimental program has been funded by the ATR National Scientific User Facility (ATR-NSUF) and by the DOE Office of Science in the framework of the Recovery Act. It has been given the name MANTRA for Measurement of Actinides Neutron TRAnsmutation.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2012

Assessment of PCMI Simulation Using the Multidimensional Multiphysics BISON Fuel Performance Code

Since 2008, the Idaho National Laboratory (INL) has been developing a next-generation nuclear fuel performance code called BISON. BISON is built using INL’s Multiphysics Object-Oriented Simulation Environment, or MOOSE. MOOSE is a massively parallel, finite element-based framework to solve systems of coupled non-linear partial differential equations using the Jacobian-FreeNewton Krylov (JFNK) method. MOOSE supports the use of complex two- and three-dimensional meshes and uses implicit time integration, which is important for the widely varied time scales in nuclear fuel simulation. MOOSE’s object-oriented architecture minimizes the programming required to add new physics models. BISON has been applied to various nuclear fuel problems to assess the accuracy of its 2D and 3D capabilities. The benchmark results used in this assessment range from simulation results from other fuel performance codes to measurements from well-known and documented reactor experiments. An example of a well-documented experiment used in this assessment is the Third Risø Fission Gas Project, referred to as “Bump Test GE7”, which was performed on rod ZX115. This experiment was chosen because it allows for an evaluation of several aspects of the code, including fully coupled thermo-mechanics, contact, and several nonlinear material models. Bump Test GE7 consists of a base-irradiation period of a full-length rod in the Quad-Cities-1 BWR for nearly 7 years to a burnup of 4.17% FIMA. The base irradiation test is followed by a “bump test” of a sub-section of the original rod. The bump test takes place in the test reactor DR3 at Risø in a water-cooled HP1 rig under BWR conditions where the power level is increased by about 50% over base irradiation levels in the span of several hours. During base irradiation, the axial power profile is flat. During the bump test, the axial power profile changes so that the bottom half of the rod is at approximately 50% higher power than at the base irradiation level, while the power at the top of the rod is at about 20% of the base irradiation power level. 2D BISON simulations of the Bump Test GE7 were run using both discrete and smeared pellet geometry. Comparisons between these calculations and experimental measurements are presented for clad diameter and elongation after the base irradiation and clad profile along the length of the test section after the bump test. Preliminary comparisons between calculations and measurements are favorable, supporting the use of BISON as an accurate multiphysics fuel simulation tool.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2015

Validation of continuous energy sensitivity coefficients calculations in the MORET 5 code - 14269

A continuous-energy sensitivity coefficients calculation capability has been developed in the MORET 5 Monte Carlo code recently. As discussed in this paper, it relies on the differential operator method, an adjoint weighting model (to avoid calculating the fission source derivatives) and a constrained sensitivity coefficient model for sensitivity profiles to distributions such as, for instance, the fission spectrum. For now, the coefficients are provided per medium, per isotope, per reaction on an energy binning defined by the user. The sensitivity coefficients are currently available for the following quantities: total, elastic scattering, total inelastic scattering, fission, total capture and radiative capture cross sections, average neutron produced by fission and fission spectrum. This paper deals with the validation of this new feature in the MORET code on several benchmarks and applications with various energy spectra and geometrical configurations. This validation is performed through the UACSA expert group and the Jezebel ICSBEP benchmarks, but also thanks to calculations performed in the frame of experimental program design in the STACY facility. Comparisons are made using the MCNP6.1 code and the SCALE6.1 package as references. Preliminary results show a pretty good agreement between the different software. (authors)

42 ENGINEERING↗
DOE OSTI2015

Monte-Carlo Simulations of the Nuclear Energy Deposition Inside the CARMEN-1P Differential Calorimeter Irradiated into OSIRIS Reactor

The nuclear heating measurements in Material Testing Reactors (MTRs) are crucial for the study of nuclear materials and fuels under irradiation. The reference measurements of this nuclear heating are especially performed by a differential calorimeter including a graphite sample material. These measurements are then used for other experimental conditions in order to predict the nuclear heating and thermal conditions induced in the irradiation devices. Nuclear heating is a great deal of interest at the moment as the measurement of such heating is an important issue for MTRs reactors. This need is especially generated by the new Jules Horowitz Reactor (JHR), under construction at CEA/Cadarache 'French Alternative Energies and Atomic Energy Commission'. This new reactor, that will be operational in late 2019, is a new facility for the nuclear research on materials and fuels. Indeed the expected nuclear heating rate is about 20 W/g for nominal capacity of 100 MW. The present Monte Carlo calculation works belong to the IN-CORE (Instrumentation for Nuclear radiation and Calorimetry On line in Reactor): a joint research program between the CEA and Aix- Marseille University in 2009. One scientific aim of this program is to design and develop a multi-sensors device, called CARMEN, dedicated to the measurements of main physical parameters simultaneously encountered inside JHR's experimental channels (core and reflector) such as neutron fluxes, photon fluxes, temperature, and nuclear heating. A first prototype was already developed. This prototype includes two mock-ups dedicated respectively to neutronic measurements (CARMEN-1N) and to photonic measurements (CARMEN-1P) with in particular a specific differential calorimeter. Two irradiation campaigns were performed successfully in the periphery of OSIRIS reactor (a MTR located at Saclay, France) in 2012 for nuclear heating levels up to 2 W/g. First Monte Carlo calculations reduced to the graphite sample of the calorimeter were carried out. A preliminary analysis shows that the numerical results overestimate the measurements by about 20 %. A new approach has been developed in order to estimate the nuclear heating by two methods (energy deposition or KERMA) by considering the whole complete geometry of the sensor. This new approach will contribute to the interpretation of the irradiation campaign and will be useful to improve the out-of-pile calibration procedure of the sensor and its thermal response during irradiations. The aim of this paper is to present simulations made by using MCNP5 Monte-Carlo transport code (using ENDF/B-VI nuclear data library) for the nuclear heating inside the different parts of the calorimeter (head, rod and base). Calculations into two steps will be realized. We will use as an input source in the model new spectra (neutrons, prompt-photons and delayed-photons) calculated with the Monte Carlo code TRIPOLI-4{sup R} inside different experimental channels (water) located into the OSIRIS periphery and used during the CARMEN-1P irradiation campaign. We will consider Neutrons- Photons-Electrons and Photons-Electrons modes. We will begin by a brief description of the differential-calorimeter device geometry. Then the MCNP5 model used for the calculations of nuclear heating inside the calorimeter elements will be introduced. The energy deposition due to the prompt-gamma, delayed-gamma and neutrons, the neutron-activation of the device will be considered. The different components of the nuclear heating inside the different parts of the calorimeter will be detailed. Moreover, a comparison between KERMA and nuclear energy deposition estimations will be given. Finally, a comparison between this total nuclear heating Calculation and Experiment in graphite sample will be determined. (authors)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2016

SU-F-T-127: Charged Particle Transport in Condensed Media

Purpose: Provide quality interaction cross sections for charged particle Monte Carlo (MC) track structure codes and evaluate low energy electron transport in condensed media. Methods: MC methods and codes are often used to model or simulate charged particle radiation transport in matter. Detailed (or event-by-event) track structure simulations are of special interest for the modeling of the physical and chemical stages of radiation action with matter and the initial radiation damage to biological systems. They require reliable interaction cross sections of all radiation qualities considered (e.g., electrons, protons, alpha particles, light and heavy ions) with the target material under consideration, mainly in the condensed phase, including liquids and solids. Interaction cross sections are calculated using the dielectric formalism, a mixture of first principles, theoretical modeling and experimental information for bulk and surface transport and implemented into MC track structure codes. Secondary electron emission yields from amorphous solid water (ASW) and thin metal foils (copper and gold) after fast proton impact are simulated and measured experimentally. Results: After considering different transport models for bulk and surface transport and a careful modeling of the experimental geometry, simulated secondary electron emission yields follow the trends of experimental data well. Furthermore, yields for electron emissions below 50 eV are sensitive to differential elastic scattering cross sections. Conclusion: Low-energy electron transport in condensed media is still a challenge for detailed track structure simulation codes. Interaction cross-sections, transport models, and target geometry need to be considered adequately. The research was funded in part by NSF Major Research Instrumentation Program 2009, Award Number: 0923270 and by NIH/NCI R01 CA93351.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

A time-parallel method for the solution of PDE-constrained optimization problems

We study a time-parallel approach to solving quadratic optimization problems with linear time-dependent partial differential equation (PDE) constraints. These problems arise in formulations of optimal control, optimal design and inverse problems that are governed by parabolic PDE models. They may also arise as subproblems in algorithms for the solution of optimization problems with nonlinear time-dependent PDE constraints, e.g., in sequential quadratic programming methods. We apply a piecewise linear finite element discretization in space to the PDE constraint, followed by the Crank-Nicolson discretization in time. The objective function is discretized using finite elements in space and the trapezoidal rule in time. At this point in the discretization, auxiliary state variables are introduced at each discrete time interval, with the goal to enable: (i) a decoupling in time; and (ii) a fixed-point iteration to recover the solution of the discrete optimality system. The fixed-point iterative schemes can be used either as preconditioners for Krylov subspace methods or as smoothers for multigrid (in time) schemes. We present promising numerical results for both use cases.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2018

Nucleus-specific expression in the multinuclear mushroom-forming fungus Agaricus bisporus reveals different nuclear regulatory programs

Many fungi are polykaryotic, containing multiple nuclei per cell. In the case of heterokaryons, there are different nuclear types within a single cell. It is unknown what the different nuclear types contribute in terms of mRNA expression levels in fungal heterokaryons. Each cell of the mushroom Agaricus bisporus contains two to 25 nuclei of two nuclear types originating from two parental strains. Using RNA-sequencing data, we assess the differential mRNA contribution of individual nuclear types and its functional impact. We studied differential expression between genes of the two nuclear types, P1 and P2, throughout mushroom development in various tissue types. P1 and P2 produced specific mRNA profiles that changed through mushroom development. Differential regulation occurred at the gene level, rather than at the locus, chromosomal, or nuclear level. P1 dominated mRNA production throughout development, and P2 showed more differentially up-regulated genes in important functional groups. In the vegetative mycelium, P2 up-regulated almost threefold more metabolism genes and carbohydrate active enzymes (cazymes) than P1, suggesting phenotypic differences in growth. We identified widespread transcriptomic variation between the nuclear types of A. bisporus. Our method enables studying nucleus-specific expression, which likely influences the phenotype of a fungus in a polykaryotic stage. Our findings have a wider impact to better understand gene regulation in fungi in a heterokaryotic state. This work provides insight into the transcriptomic variation introduced by genomic nuclear separation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

BISON Robustness and Performance Improvements

BISON is a modern finite-element based nuclear fuel performance code that has been under development at the Idaho National Laboratory (USA) since 2009 [1]. The code is applicable to both steady and transient fuel behavior and can be used to analyze 1D (spherically symmetric), 2D (axisymmetric and generalized plane strain) or 3D geometries. BISON is the fuel performance code used within CASL for LWR fuel under both normal operating and accident conditions. BISON is built using the INL Multiphysics ObjectOriented Simulation Environment, or MOOSE [2, 3]. MOOSE is a massively parallel, finite element-based framework to solve systems of coupled non-linear partial differential equations using the Jacobian-Free Newton Krylov (JFNK) method [4]. This enables investigation of computationally large problems, for example a full stack of discrete pellets in a LWR fuel rod, or every rod in a full reactor core. MOOSE supports the use of complex two and three-dimensional meshes and uses implicit time integration, important for the widely varied time scale in nuclear fuel simulation. An object-oriented architecture is employed which greatly minimizes the programming effort required to add new material and behavioral models. The flexibility of the implicit and fully coupled multiphysics approach comes with a need for constructing suitable approximations for the Jacobian matrix of the coupled system used for either preconditioning a Krylov solve or in a direct Newton solve. Preconditioning options for Bison problems need to be revisited with new preconditioning methods becoming available.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2017

Conceptualizing strategic environmental assessment: Principles, approaches and research directions

Increasing emphasis has been placed in recent years on transitioning strategic environmental assessment (SEA) away from its environmental impact assessment (EIA) roots. Scholars have argued the need to conceptualize SEA as a process designed to facilitate strategic thinking, thus enabling transitions toward sustainability. The practice of SEA, however, remains deeply rooted in the EIA tradition and scholars and practitioners often appear divided on the nature and purpose of SEA. This paper revisits the strategic principles of SEA and conceptualizes SEA as a multi-faceted and multi-dimensional assessment process. It is suggested that SEA can be conceptualized as series of approaches operating along a spectrum from less to more strategic – from impact assessment-based to strategy-based – with each approach to SEA differentiated by the specific objectives of SEA application and the extent to which strategic principles are reflected in its design and implementation. Advancing the effectiveness of SEA requires a continued research agenda focused on improving the traditional SEA approach, as a tool to assess the impacts of policies, plans and programs (PPPs). Realizing the full potential of SEA, however, requires a new research agenda — one focused on the development and testing of a deliberative governance approach to SEA that can facilitate strategic innovations in PPP formulation and drive transitions in short-term policy and initiatives based on longer-term thinking. - Highlights: • SEA facilitates strategic thinking, enabling transitions toward sustainability. • SEA is conceptualized as a spectrum of approaches, from IA-based to strategy-based. • Each approach variably emphasizes strategic principles in its design and practice. • There is no one conceptualization of SEA that is best, SEA is fit for PPP purpose. • Research is needed to advance SEA to facilitate strategic PPP transformations.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

A proteome-wide assessment of the oxidative stress paradigm for metal and metal-oxide nanomaterials in human macrophages

Responsible implementation of engineered nanomaterials (ENMs) into commercial applications is an important societal issue, driving demand for new approaches for rapid and comprehensive evaluation of their bioactivity and safety. An essential part of any research focused on identifying potential hazard of ENMs is the appropriate selection of biological endpoints to evaluate. Herein, we use a tiered strategy employing both targeted biological assays and untargeted quantitative proteomics to elucidate the biological responses of human macrophages across a library of metal/metal oxide ENMs, raised as priority ENMs for investigation by NIEHS’s Nanomaterial Health Implications Research (NHIR) program. Our results show that quantitative cellular proteome profiles readily distinguish ENM types based on their cytotoxic potential according to induction of biological processes and pathways involved in the cellular antioxidant response, TCA cycle, oxidative stress, endoplasmic reticulum stress, and immune responses as major processes impacted. Interestingly, pathway analysis of differentially abundant proteins also revealed new cell processes that were influenced by all ENMs independent of cytotoxic potential. These included pathways previously implicated as cellular adaptive mechanisms to low levels of oxidative stress, including cell adhesion, protein translation and protein targeting pathways. Unsupervised clustering of all data revealed the most striking proteome changes that differentiated ENM classes involved a small subset of proteins involved in the oxidative stess response (HMOX1), protein chaperone functions (HS71B, DNJB1), and autophagy (SQSTM), providing a potential new panel of markers of ENM-induced cell stress. To our knowledge, the results represent the most comprehensive profiling of the biological responses to a library of ENMs conducted using quantitative mass spectrometry-based proteomics. The results provide a basis to identify the patterns of a diverse set of cellular pathways and cell processes impacted by ENM exposure in an important immune cell type, laying the foundation for multivariate, pathway-level structure activity assessments of ENMs in the future.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Covariation of Slab Tracers, Volatiles, and Oxidation During Subduction Initiation

Abstract Subduction‐related lavas have higher Fe 3+ /∑Fe than midocean ridge basalts (MORB). Hypotheses for this offset include imprint from subducting slabs and differentiation in thickened crust. These ideas are readily tested through examination of the time‐dependent evolution of slab‐derived signatures, thickening crust of the overriding plate, and evolving redox during subduction initiation. Here, we present Fe 3+ /ΣFe and volatile element abundances of volcanic glasses recovered from International Ocean Discovery Program (IODP) Expedition 352 to the Izu‐Bonin‐Mariana (IBM) forearc. The samples include forearc basalts (FAB) that are stratigraphically overlain by low‐ and high‐silica boninite lavas. The FAB glasses have 0.18–0.85 wt% H 2 O, 75–233 ppm CO 2 , S contents controlled by saturation with a sulfide phase (602–1,386 ppm), Ba/La from 3.9‐10, and Fe 3+ /ΣFe ratios from 0.136 to 0.177. These compositions are similar to MORB and suggest that decompression melting of dry and reduced mantle dominates the earliest stages of subduction initiation. Low‐ and high‐silica boninite glasses have 1.51–3.19 wt% H 2 O, CO 2 below detection, S contents below those required for sulfide saturation (5–235 ppm), Ba/La from 11 to 29, and Fe 3+ /∑Fe from 0.181 to 0.225. The compositions are broadly similar to modern arc lavas in the IBM arc. These data demonstrate that the establishment of fluid‐fluxed melting of the mantle, which occurs in just 0.6–1.2 my after subduction initiation, is synchronous with the production of oxidized, mantle‐derived magmas. The coherence of high Fe 3+ /∑Fe and Ba/La ratios with high H 2 O contents in Expedition 352 glasses and the modern IBM arc rocks strongly links the production of oxidized arc magmas to signatures of slab dehydration.

Brounce, Maryjo↗
DOE OSTI2015

SU-E-J-248: Contributions of Tumor and Stroma Phenotyping in Computer-Aided Diagnosis

Purpose: To gain insight into the role of parenchyma stroma in the characterization of breast tumors by incorporating computerized mammographic parenchyma assessment into breast CADx in the task of distinguishing between malignant and benign lesions. Methods: This study was performed on 182 biopsy-proven breast mass lesions, including 76 benign and 106 malignant lesions. For each full-field digital mammogram (FFDM) case, our quantitative imaging analysis was performed on both the tumor and a region-of-interest (ROI) from the normal contralateral breast. The lesion characterization includes automatic lesion segmentation and feature extraction. Radiographic texture analysis (RTA) was applied on the normal ROIs to assess the mammographic parenchymal patterns of these contralateral normal breasts. Classification performance of both individual computer extracted features and the output from a Bayesian artificial neural network (BANN) were evaluated with a leave-one-lesion-out method using receiver operating characteristic (ROC) analysis with area under the curve (AUC) as the figure of merit. Results: Lesion characterization included computer-extracted phenotypes of spiculation, size, shape, and margin. For parenchymal pattern characterization, five texture features were selected, including power law beta, contrast, and edge gradient. Merging of these computer-selected features using BANN classifiers yielded AUC values of 0.79 (SE=0.03) and 0.67 (SE=0.04) in the task of distinguishing between malignant and benign lesions using only tumor phenotypes and texture features from the contralateral breasts, respectively. Incorporation of tumor phenotypes with parenchyma texture features into the BANN yielded improved classification performance with an AUC value of 0.83 (SE=0.03) in the task of differentiating malignant from benign lesions. Conclusion: Combining computerized tumor and parenchyma phenotyping was found to significantly improve breast cancer diagnostic accuracy highlighting the need to consider both tumor and stroma in decision making. Funding: University of Chicago Dean Bridge Fund, NCI U24-CA143848-05, P50-CA58223 Breast SPORE program, and Breast Cancer Research Foundation. COI: MLG is a stockholder in R2 technology/Hologic and receives royalties from Hologic, GE Medical Systems, MEDIAN Technologies, Riverain Medical, Mitsubishi, and Toshiba. MLG is a cofounder and stockholder in Quantitative Insights.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Highly efficient Cas9-mediated transcriptional programming

The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. Here we describe an improved transcriptional regulator through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. Here, we demonstrate its utility in activating endogenous coding and non-coding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Creb5 controls its own expression and directly induces the joint interzone regulatory program

Prior studies have indicated that the transcription factor Creb5 is expressed in the joint interzone, which contains the progenitors for all synovial joint tissues in both mouse and human embryos. In the absence of Creb5 function, most synovial joint interzones fail to form and the cartilage templates in the long bones remain fused. This earlier work did not clarify whether Creb5 initiates a cascade of signaling molecules, such as growth and differentiation factor 5 (Gdf5) and Wnt-family members, that in turn induce the formation of the joint interzone, or instead directly activates the expression of joint interzone markers. In the present study, an integrative analysis of the transcriptome, chromatin accessibility, and Creb5-occupancy in joint progenitors revealed that Creb5 directly binds to both its own two promoters and to the regulatory regions of Gdf5 and Sfrp2, each of whose expression in the joint interzone is Creb5-dependent. Functional enhancer analysis indicated that Creb5 binding sites in either the two Creb5 promoters, or in Gdf5 and Sfrp2 regulatory elements are necessary for these sequences to drive transgene expression in the developing synovial joints. While Creb5 directly drives Gdf5 and Sfrp2 expression in the inner joint interzone, Creb5 activates Barx1 expression specifically in the outer joint interzone. Our findings indicate that Creb5 initiates a regulatory network that both promotes the formation of synovial joints, and subsequently activates distinct transcriptional targets in the inner versus the outer regions of the joint interzone, thus regionalizing gene expression in the developing joint.

Zhang, Cheng-Hai↗