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Machine Learning to Select Experiments Driven by Fundamental Science and Applications for Targeted Nuclear Data Improvement

This work describes a blueprint for a process that accelerates progress in science by quantitatively answering the following question: What is the optimal combination of fundamental-science and application-driven experiments to maximally reduce pertinent data uncertainties? Answering this question entails solving a high-dimensional and complex optimization problem that is best solved with advanced statistic techniques often classified as machine learning. We apply this process within the framework of nuclear data with the aim to select an experiment combination that will reduce uncertainties in 239 Pu nuclear data for neutron energies between 1 and 600 keV. In this field, fundamental-physics driven data, called differential, look at one nuclear physics observable at a time. They are contrasted to application-driven, integral, data where one or few resulting values inform a broad set of nuclear data across several nuclides and energies. The candidates for integral experiments are criticality measurements that were refined by a genetic algorithm to be maximally sensitive to 239 Pu fission cross sections in the desired energy range. Twenty-three candidate differential experiments were investigated and span multiple nuclear physics observables (e.g., total, capture cross sections) for isotopes appearing in the integral experiments. The optimal combination among these candidate experiments was investigated via generalized least squares fitting, augmented with Gaussian processes to ameliorate statistical irregularities in data, and the D-optimality criterion. The latter evaluates for each pair of candidates the joint reduction in uncertainties of all 12200 nuclear data appearing in the integral experiments compared to the knowledge we have from 168 past experiments, theory, and nuclear data. We chose as differential measurements those that investigate 63 Cu and 239 Pu total cross sections, based on D-optimality rank and feasibility constraints. Two integral (criticality) experiments were selected: An experiment with Al 2 ⁢O 3 and graphite interleaved with Pu and a thick Cu reflector explores 1–30 keV, while we target the 30–600 keV range with an experiment that swaps boron in place of graphite with a different geometry.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Novel Approaches to Cellular Transplantation from the US Space Program

Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.

Pellis, Neal R.↗

Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is classified as a Category C priority pathogen (Coronaviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV [NCBITAXON:1335626] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750], human bronchial epithelial cells ["Calu-3 clone 2B4"; BTO:0002022], primary human fibroblasts ["FB"; BTO:0000452], primary human airway epithelial cells ["HAE"; BTO:0005571], human microvascular endothelial cells ["HMVE"; BTO:0003123], and whole mouse lung [BTO:0000763] tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

Crosscutting Recombination Metrology for Expediting VOC Engineering

Work carried out under this grant addressed the need for improved materials and device characterization of solar cell designs. This experimental program aimed to develop joint electrical and optical studies of solar cells based on the group-II-VI semiconductor CdTe and the chalcogenide semiconductor Cu(InGa)Se 2 . Electrical measurements focused on temperature (T) and illumination intensity (I) dependence of the open-circuit voltage (VOC), a quantity that plays an important role in conversion efficiency. The VOC depends on temperature and illumination intensity through the energy gap and positions of the quasiFermi levels (QFLs). Optical measurements exploited the illumination and temperature dependence of absolute photoluminescence (PL) intensity (PL-I), a quantity that also depends on the QFL positions. The QFL splitting is a quantity that also depends on recombination rates within the solar cell, including radiative and non-radiative processes. Other factors affect the electrical and optical properties. These include band offsets at both the front and back interfaces of the device active region where electrical contacts are formed. Understanding, locating, and quantifying the recombination properties of the solar cells was the principal goal of this research. Custom simulations were developed to solve continuity and Poisson equations selfconsistently to obtain free-electron and free-hole concentrations. The measurements of temperature and intensity dependent VOC and PL-I allowed the extraction of a number of physical parameters including the conduction band offset, the shunt constant, and the effective capture coefficient for recombination centers, both within the absorber and at the absorber-buffer interface. In addition, the back-contact barrier height is determined from electrical properties. Each of these is discussed in the report. The illumination intensity dependence of VOC and PL-I do not overlap in experiments primarily because PL is not observed in the low-intensity regime where VOC is studied. Absolute PL-I measurements enabled development of an approach directly comparing it with VOC. This in turn allowed development of a simulation capability that would consistently use both measurements, as functions of T and I, for producing a minimization scheme using a differential evolution algorithm. The approach was applied to both CdTe and Cu(InGa)Se 2 solar cells each prepared under various conditions. Shunt conductivity, QFL splitting, recombination were measured. Also extensively studied are current-voltage and frequency-dependent capacitance voltage. Work completed under this grant included studies of magnesium zinc oxide (MZO) buffered CdTe solar cells including the effects of hydroiodic acid (HI) treatment. From these studies the recombination rates were quantified at the buffer/absorber (front) interface. The effect of back-contact barrier height was investigated. CdTe solar cells were prepared with CdSe and CdS buffer layers. Lower grain-boundary potential fluctuation, higher back-contact barrier height, and greater bulk recombination were observed in early devices with CdSe buffer layer. Investigations were also carried out into CdS/Cu(InGa)Se 2 solar cells. A metal-insulatorsemiconductor capacitance-voltage technique was developed to extract recombinationrelevant properties of the absorber interface. From this work the density of interface states D it , their capture cross-section σ, fixed charge at the interface Q f , and surface recombination velocity were all extracted.

14 SOLAR ENERGY↗

Specific photoaffinity labeling of two plasma membrane polypeptides with an azido auxin

Plasma membrane vesicles were isolated from zucchini (Cucurbita pepo) hypocotyl tissue by aqueous phase partitioning and assessed for homogeneity by the use of membrane-specific enzyme assays. The highly pure (ca. 95%) plasma membrane vesicles maintained a pH differential across the membrane and accumulated a tritiated azido analogue of 3-indoleacetic acid (IAA), 5-azido-[7-3H]IAA ([3H]N3IAA), in a manner similar to the accumulation of [3H]IAA. The association of the [3H]N3IAA with membrane vesicles was saturable and subject to competition by IAA and auxin analogues. Auxin-binding proteins were photoaffinity labeled by addition of [3H]N3IAA to plasma membrane vesicles prior to exposure to UV light (15 sec; 300 nm) and detected by subsequent NaDodSO4/PAGE and fluorography. When the reaction temperature was lowered to -196 degrees C, high-specific-activity labeling of a 40-kDa and a 42-kDa polypeptide was observed. Triton X-100 (0.1%) increased the specific activity of labeling and reduced the background, which suggests that the labeled polypeptides are intrinsic membrane proteins. The labeled polypeptides are of low abundance, as expected for auxin receptors. Further, the addition of IAA and auxin analogues to the photoaffinity reaction mixture resulted in reduced labeling that was qualitatively similar to their effects on the accumulation of radiolabeled IAA in membrane vesicles. Collectively, these results suggest that the radiolabeled polypeptides are auxin receptors. The covalent nature of the label should facilitate purification and further characterization of the receptors.

NASA Discipline Number 29-20↗

MOOSE Reactor Module Meshing Enhancements to Support Reactor Physics Analysis

The U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) program develops an integrated suite of advanced reactor physics tools built upon the Multiphysics Object-Oriented Simulation Environment (MOOSE) framework. Each code generally requires an input finite element mesh on which the physics solution is calculated, reported, and transferred to other physics codes. The meshing process is often burdensome for the complex geometries present in reactors due to lack of easy-to-use, open-source meshing tools. To address the bottleneck associated with meshing complex geometries found in nuclear reactors, NEAMS initiated the development of the MOOSE Reactor Module starting in FY21. The Reactor Module builds off the existing MOOSE Mesh System to include targeted meshing capabilities such as the ability to generate hexagonal pin cells, assemblies with ducts, rotating control drums, cores, peripheral zones around a core, as well as the automatic labeling (“reporting IDs”) of pin, assembly, and planar zones to simplify post-processing of results. As a Physics Module in MOOSE, the Reactor Module is open-source, available with any MOOSE installation, directly compatible with MOOSE-based tools, and can be invoked from MOOSEbased applications to generate meshes. Functionality from the Reactor Module has been applied to several advanced reactor concepts to demonstrate user workflow improvements and accuracy. The primary objective of the Reactor Module is to improve useability of MOOSEbased tools by streamlining mesh generation and output inspection processes. During FY22, the functionality of the Reactor Module (and accompanying Mesh System) has been expanded based on user needs. First, the Reactor Geometry Mesh Builder capability developed primarily in FY21 has been refactored and merged to the public MOOSE repository. This capability wraps underlying Reactor Module mesh generators into a “Pin – Assembly – Core” workflow appropriate for conventional Cartesian and hexagonal geometries, and notably assigns material IDs during mesh generation stage and generates only the minimal number of blocks needed in order to reduce computational burden. Biasing and boundary layer options have been added to the base mesh generators as required by thermal hydraulics solvers. The reporting ID functionality has been expanded to differentiate ring-wise and azimuthal sectors within a pin for use with depletion algorithms, and VectorPostProcessor and Reporter objects are now available to integrate solution variables across zones based on ID combinations. Functionality to trim hexagonal meshes along the center or periphery has been developed so users may leverage symmetry and reflective boundary conditions to reduce the mesh size. A flexible and powerful tool to fill the space between two sidesets has been introduced to the framework and can be used for transition layers such as stitching two assemblies together with different numbers of pins, or for complex geometries which do not follow conventional Cartesian/hexagonal patterns. Finally, additional verification problems were performed with NEAMS physics tools in complement with existing NEAMS work.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Measurements of Neutron Scattering from a Copper Sample Using a Quasi-Differential Method in the Region from 2 keV to 20 MeV

Neutron scattering from a copper sample was measured at Rensselaer Polytechnic Institute utilizing the quasi-differential method. The measurement spanned the energy range from 0.5 to 20 MeV using the high-energy scattering system and from 2 keV to 0.5 MeV using the new mid-energy scattering system. Copper was selected as a material of interest to measure due to large discrepancies between experiments and simulations of the Zeus benchmark. The Zeus benchmark consists of a copper reflected highly enriched uranium system, and the angular distribution of copper scattering was thought to potentially be the cause of the discrepancy. The copper measurements found differences in the scattering response particularly in the incident energy region from 1 to 2 MeV for the high-energy measurement and from 2 to 4 keV in the mid-energy system. These differences are particularly noticeable at angles near 90 deg in the high-energy system and back angles in the mid-energy system. Additionally, for ENDF/B-VIII.0 there is a large discrepancy at the forward angle in the energy range around 0.5 MeV. For these reasons, a new evaluation of copper scattering utilizing these results is recommended and perhaps could help to improve the agreement with the Zeus benchmarks.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

A statistical model of diurnal variation in human growth hormone

The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

Non-NASA Center↗

Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear

We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.

NASA Discipline Number 40-10↗

Sensitivity Studies, Gap Analysis, and Benchmark Experiment Optimization for Reactor Physics and Criticality Safety Applications

Many new reactor designs, such as advanced reactors and micro reactors, have materials that lack nuclear data validation. This is also true for many other applications in criticality safety and global security. Both differential and integral experiments are needed to validate cross-section data. Without this, a user cannot have confidence in the predicted results of a radiation-transport code. This work describes an approach called ARCHIMEDES (Application Relevant Critical/Subcritical HEU/Pu-based Integral Measurements for Enhancing Data and Evaluating Sensitivities) to design new criticality experiments that have similar k eff cross-section sensitivities to an application of interest. This process involves simulations to generate cross-section sensitivities to a parameter of interest (such as k eff ), a gap analysis to determine which existing benchmarks are most similar to the application, and an experiment optimization. Recently, there has been a great deal of interest in the reactor physics community on advanced reactors, micro reactors, and accelerator driven systems (ADS). This work will apply the described method to specific examples in this area. The focus of this work will be on the sensitivity study and gap analysis, while future work will include experiment design.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Reflectance spectroscopy of ferric sulfate-bearing montmorillonites as Mars soil analog materials

Spectroscopic analyses have shown that smectites enhanced in the laboratory with additional ferric species exhibit important similarities to those of the soils on Mars. Ferrihydrite in these chemically treated smectites has features in the visible to near-infrared region that resemble the energies and band strengths of features in reflectance spectra observed for several bright regions on Mars. New samples have been prepared with sulfate as well, because S was found by Viking to be a major component in the surface material on Mars. A suite of ferrihydrite-bearing and ferric sulfate-bearing montmorillonites, prepared with variable Fe3+ and S concentrations and variable pH conditions, has been analyzed using reflectance spectroscopy in the visible and infrared regions, Mossbauer spectroscopy at room temperature and 4 K, differential thermal analysis, and X-ray diffraction. These analyses support the formation of ferrihydrite of variable crystallinity in the ferrihydrite-bearing montmorillonites and a combination of schwertmannite and ferrihydrite in the ferric sulfate-bearing montmorillonites. Small quantities of poorly crystalline or nanophase forms of other ferric materials may also be present in these samples. The chemical formation conditions of the ferrihydrite-bearing and ferric sulfate-bearing montmorillonites influence the character of the low temperature Mossbauer sextets and the visible reflectance spectra. An absorption minimum is observed at 0.88-0.89 micrometers in spectra of the ferric sulfate-bearing samples, and at 0.89-0.92 micrometers in spectra of the ferrihydrate-bearing montmorillonites. Mossbauer spectra of the ferric sulfate-bearing montmorillonites indicate variable concentrations of ferrihydrite and schwertmannite in the interlaminar spaces and along grain surfaces. Dehydration under reduced atmospheric pressure conditions induces a greater effect on the adsorbed and interlayer water in ferrihydrite-bearing montmorillonite than on the water in ferric sulfate-bearing montmorillonite. Reflectance spectra of ferric sulfate-bearing montmorillonite include a strong 3-micrometers band that is more resistant to dry atmospheric conditions than the 3-micrometers band in spectra of similarly prepared ferrihydrite-bearing montmorillonites.

NASA Discipline Exobiology↗

Neutron Leakage Spectra of the EUCLID Experiment [Abstract]

Integral experiments with sub-critical and critical configurations of special nuclear material are performed in support of nuclear data validation and adjustment. Different nuclear data evaluations may have different values for individual cross sections due to uncertainties in (or lack of) differential experiments, but compensating errors in these data sets can lead to the same k eff results for one application while vastly different for another application. One example of this is 239 Pu, where both ENDF/B-VIII.0 and JEFF-3.3 correctly compute k eff of the Jezebel critical assembly, but the individual contributions from each reaction are vastly different. To help resolve this specific case, the Experiments Underpinned by Computational Learning for Improvements in Nuclear Data (EUCLID) project used machine learning to design a set of experiments to help resolve the compensating errors in 239 Pu. A total of six responses were measured during the experimental campaign, which constrain the data in ways that k eff alone cannot and will be used for adjustment of the nuclear data. One of these responses is the neutron leakage spectrum, which recent work has shown to be useful for constraining the prompt fission neutron spectrum and inelastic scattering. The neutron leakage spectra were measured utilizing a 3 in. right cylinder EJ-301D detector. The measured signal in the detector was deconvoluted using spectrum unfolding techniques, which are presented and compared to simulations.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Two-stage model of radon-induced malignant lung tumors in rats: effects of cell killing

A two-stage stochastic model of carcinogenesis is used to analyze lung tumor incidence in 3750 rats exposed to varying regimens of radon carried on a constant-concentration uranium ore dust aerosol. New to this analysis is the parameterization of the model such that cell killing by the alpha particles could be included. The model contains parameters characterizing the rate of the first mutation, the net proliferation rate of initiated cells, the ratio of the rates of cell loss (cell killing plus differentiation) and cell division, and the lag time between the appearance of the first malignant cell and the tumor. Data analysis was by standard maximum likelihood estimation techniques. Results indicate that the rate of the first mutation is dependent on radon and consistent with in vitro rates measured experimentally, and that the rate of the second mutation is not dependent on radon. An initial sharp rise in the net proliferation rate of initiated cell was found with increasing exposure rate (denoted model I), which leads to an unrealistically high cell-killing coefficient. A second model (model II) was studied, in which the initial rise was attributed to promotion via a step function, implying that it is due not to radon but to the uranium ore dust. This model resulted in values for the cell-killing coefficient consistent with those found for in vitro cells. An "inverse dose-rate" effect is seen, i.e. an increase in the lifetime probability of tumor with a decrease in exposure rate. This is attributed in large part to promotion of intermediate lesions. Since model II is preferable on biological grounds (it yields a plausible cell-killing coefficient), such as uranium ore dust. This analysis presents evidence that a two-stage model describes the data adequately and generates hypotheses regarding the mechanism of radon-induced carcinogenesis.

NASA Program Radiation Health↗

Effects of physical agitation on yield of greenhouse-grown soybean

Agronomic and horticultural crop species experience reductions in growth and harvestable yield after exposure to physical agitation (also known as mechanical stress), as by wind or rain. A greenhouse study was conducted to test the influence of mechanical stress on soybean yield and to determine if exposure to mechanical stress during discrete growth periods has differential effects on seed yield. A modified rotatory shaker was used to apply seismic (i.e., shaking) stress. Brief, periodic episodes of seismic stress reduced stem length, total seed dry weight, and seed number of soybean [Glycine max (L.) Merr.]. Lodging resistance was greater for plants stressed during vegetative growth or throughout vegetative and reproductive growth than during reproductive growth only. Seed dry weight yield was reduced regardless of the timing or duration of stress application, but was lowest when applied during reproductive development. Seismic stress applied during reproductive growth stages R1 to R2 (Days 3 to 4) was as detrimental to seed dry weight accumulation as was stress applied during growth stages R1 to R6 (Days 39 to 42). Seed dry weight per plant was highly correlated with seed number per plant, and seed number was correlated with the seed number of two- and three-seeded pods. Dry weight per 100 seeds was unaffected by seismic-stress treatment. Growth and yield reductions resulting from treatments applied only during the vegetative stage imply that long-term mechanical effects were induced, from which the plants did not fully recover. It is unclear which yield-controlling physiological processes were affected by mechanical stress. Both transient and long-term effects on yield-controlling processes remain to be elucidated.

Non-NASA Center↗

Natural and Engineered Features Supporting Environmental Performance of Idaho National Laboratory’s Remote-Handled Low-Level Waste Disposal Facility

The Idaho National Laboratory’s (INL’s) Remote-Handled Low-Level Waste (RH LLW) Disposal Facility has been designed and constructed to receive waste generated at the INL site in support of the U.S. Department of Energy (DOE) Office of Nuclear Energy (NE) and Naval Reactors (NR) missions. The facility has been designed to receive legacy RH LLW currently in storage at INL facilities and new waste generated by nuclear research programs. RH LLW to be received at the facility is solid waste consisting of surface contaminated debris; ion exchange resins used to purify cooling and canal water; activated metals generated during reactor core change outs and Naval spent fuel management; and nuclear Research & Development. Disposal of INL's RH LLW poses unique disposal challenges due to high radiation levels (contact rates up to 600 Sv/hr [60,000 Rem/hr]) that require remote handling and adequate shielding for transportation and disposal. The facility has been designed to meet the requirements of DOE Order 435.1 [1], including the all-pathways dose, air pathway dose, inadvertent intruder doses, and radon emissions limits. This paper presents an overview of natural and engineered design features that support the safety case and enhance the environmental performance of the facility. These include location selection, use of reinforced pre-cast concrete vaults; a robust hydraulic drainage system; use of steel waste canisters for waste disposal; the facility monitoring system; facility layout; and crediting waste forms. The facility performance assessment (PA) [2] developed to meet the requirements of DOE Order 435.1 “Radioactive Waste Management” credits each of these protective features. Releases from waste forms disposed of at this facility are limited by corrosion of the steel waste canisters which will ultimately allow contact with infiltrating water followed by transport of radionuclides from the vault system. The steel waste canisters were credited for their ability to limit water contact with the waste based on the demonstrated ability of the reinforced pre-caste concrete vaults to provide long-term structural protection of the steel waste canisters. Verification of hydraulic and concrete performance was conducted through laboratory data, field infiltration tests supported by a robust monitoring system, and numerical modeling. Releases into the vault system from activated metals are based on site-specific corrosion data. Radionuclide transport from the vault system from all waste forms is based on site-specific climatological, hydrologic, and stratigraphic data. At INL, the groundwater pathway historically and appropriately has received the most attention. By crediting aspects of the natural system, the engineered vault system, and the waste, estimated radiologic doses via the groundwater pathway are minimal. Air pathway doses were reduced by differentially crediting corrosion of aluminum and stainless steel activated metals resulting in the pathway being screened out of the PA. Groundwater and inadvertent intruder doses were reduced through selective facility layout. This paper provides an overview of the system-wide protective features incorporated into the facility design along with an extensive reference list to supporting technical papers and analyses that provide data and interpretation.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

NASA Discipline Regulatory Physiology↗

Light differentially regulates cell division and the mRNA abundance of pea nucleolin during de-etiolation

The abundance of plant nucleolin mRNA is regulated during de-etiolation by phytochrome. A close correlation between the mRNA abundance of nucleolin and mitosis has also been previously reported. These results raised the question of whether the effects of light on nucleolin mRNA expression were a consequence of light effects on mitosis. To test this we compared the kinetics of light-mediated increases in cell proliferation with that of light-mediated changes in the abundance of nucleolin mRNA using plumules of dark-grown pea (Pisum sativum) seedlings. These experiments show that S-phase increases 9 h after a red light pulse, followed by M-phase increases in the plumule leaves at 12 h post-irradiation, a time course consistent with separately measured kinetics of red light-induced increases in the expression of cell cycle-regulated genes. These increases in cell cycle-regulated genes are photoreversible, implying that the light-induced increases in cell proliferation are, like nucleolin mRNA expression, regulated via phytochrome. Red light stimulates increases in the mRNA for nucleolin at 6 h post-irradiation, prior to any cell proliferation changes and concurrent with the reported timing of phytochrome-mediated increases of rRNA abundance. After a green light pulse, nucleolin mRNA levels increase without increasing S-phase or M-phase. Studies in animals and yeast indicate that nucleolin plays a significant role in ribosome biosynthesis. Consistent with this function, pea nucleolin can rescue nucleolin deletion mutants of yeast that are defective in rRNA synthesis. Our data show that during de-etiolation, the increased expression of nucleolin mRNA is more directly regulated by light than by mitosis.

NASA Program Fundamental Space Biology↗

Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion

Arterial regions exposed to oscillatory shear (OS) in branched arteries are lesion-prone sites of atherosclerosis, whereas those of laminar shear (LS) are relatively well protected. Here, we examined the hypothesis that OS and LS differentially regulate production of O2- from the endothelial NAD(P)H oxidase, which, in turn, is responsible for their opposite effects on a critical atherogenic event, monocyte adhesion. We used aortic endothelial cells obtained from C57BL/6 (MAE-C57) and p47phox-/- (MAE-p47-/-) mice, which lack a component of NAD(P)H oxidase. O2- production was determined by dihydroethidium staining and an electron spin resonance using an electron spin trap methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Chronic exposure (18 h) to an arterial level of OS (+/- 5 dynes/cm2) increased O2- (2-fold) and monocyte adhesion (3-fold) in MAE-C57 cells, whereas chronic LS (15 dynes/cm2, 18 h) significantly decreased both monocyte adhesion and O2- compared with static conditions. In contrast, neither LS nor OS were able to induce O2- production and monocyte adhesion to MAE-p47-/-. Treating MAE-C57 with a cell-permeable superoxide dismutase compound, polyethylene glycol-superoxide dismutase, also inhibited OS-induced monocyte adhesion. In addition, over-expressing p47phox in MAE-p47-/- restored OS-induced O2- production and monocyte adhesion. These results suggest that chronic exposure of endothelial cells to OS stimulates O2- and/or its derivatives produced from p47phox-dependent NAD(P)H oxidase, which, in turn, leads to monocyte adhesion, an early and critical atherogenic event.

NASA Program Fundamental Space Biology↗