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At least 883 records · Page 49

Enhanced Hanford Low-Activity Waste Glass Property Data Development: Phase 2

This report summarizes and analyzes the data collected on a second test matrix of 42 low-activity waste (LAW) glass compositions intended to expand the LAW glass composition region over which glass property-composition models are valid. The 42 LAW glass compositions were selected using a statistical layered experimental design approach to explore a new glass composition region that overlaps and expands beyond the previously explored LAW glass composition region. The layered design of 42 LAW glasses consisted of 21 outer-layer glasses, 15 inner-layer glasses, a center glass (three replicates), and two glasses previously tested at another laboratory. The outer-layer glass compositions include extrema based on current projections of the LAW feeds and melter operating temperatures. One of the outer-layer compositions was eliminated due to the inability to form a glass. Therefore, only 41 glasses were analyzed. The analyses performed on these glasses include chemical composition (for target compositional verification), density, viscosity, electrical conductivity, crystal fraction, canister centerline cooling with crystal identification, the Product Consistency Test, sulfur solubility, and the Vapor Hydration Test. This report discusses in depth the results obtained from this testing.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Enhanced Hanford Low-Activity Waste Glass Property Data Development: Phase 2

This report summarizes and analyzes the data collected on a second test matrix of 42 low-activity waste (LAW) glass compositions intended to expand the LAW glass composition region over which glass property-composition models are valid. The 42 LAW glass compositions were selected using a statistical layered experimental design approach to explore a new glass composition region that overlaps and expands beyond the previously explored LAW glass composition region. The layered design of 42 LAW glasses consisted of 21 outer-layer glasses, 15 inner-layer glasses, a center glass (three replicates), and two glasses previously tested at another laboratory. The outer-layer glass compositions include extrema based on current projections of the LAW feeds and melter operating temperatures. One of the outer-layer compositions was eliminated due to the inability to form a glass. Therefore, only 41 glasses were analyzed. The analyses performed on these glasses include chemical composition (for target compositional verification), density, viscosity, electrical conductivity, crystal fraction, canister centerline cooling with crystal identification, the Product Consistency Test, sulfur solubility, and the Vapor Hydration Test. This report discusses the results obtained from this testing.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

How well do CMIP5 climate simulations replicate historical trends and patterns of droughts?

Assessing the uncertainties and understanding the deficiencies of climate models are fundamental to developing adaptation strategies. The objective of this study is to understand how well Coupled Model Intercomparison-Phase 5 (CMIP5) climate model simulations replicate ground-based observations of continental drought areas and their trends. The CMIP5 multimodel ensemble encompasses the Climatic Research Unit (CRU) ground-based observations of area under drought at all time steps. However, most model members overestimate the areas under extreme drought, particularly in the Southern Hemisphere (SH). Furthermore, the results show that the time series of observations and CMIP5 simulations of areas under drought exhibit more variability in the SH than in the Northern Hemisphere (NH). The trend analysis of areas under drought reveals that the observational data exhibit a significant positive trend at the significance level of 0.05 over all land areas. The observed trend is reproduced by about three-fourths of the CMIP5 models when considering total land areas in drought. While models are generally consistent with observations at a global (or hemispheric) scale, most models do not agree with observed regional drying and wetting trends. Over many regions, at most 40% of the CMIP5 models are in agreement with the trends of CRU observations. The drying/wetting trends calculated using the 3 months Standardized Precipitation Index (SPI) values show better agreement with the corresponding CRU values than with the observed annual mean precipitation rates. As a result, pixel-scale evaluation of CMIP5 models indicates that no single model demonstrates an overall superior performance relative to the other models.

54 ENVIRONMENTAL SCIENCES↗

Integrated ‘omics analysis for studying the microbial community response to a pH perturbation of a cellulose-degrading bioreactor culture

Propionate accumulation is a common indicator of process imbalances in anaerobic bioreactor systems. The accumulation of propionate can occur due to low retention rates, hydrogen accumulation, or mechanical changes affecting the proximity between propionate oxidizers and partner species, thereby preventing necessary electron transfer. Few studies, however, have observed the changes in microbial community structure during propionate accumulation. We used 454 pyrosequencing of 16S rDNA to evaluate the community membership during propionate accumulations in replicate bioreactors with rumen based cultures. Half of the culture volume from a parent reactor was transferred to a sterile “daughter” reactor, and both systems were run identically. Both reactors experienced a propionate accumulation after roughly 10 days, with the propionate accumulation being less pronounced in the parent reactor as compared to the daughter reactor. Non-metric multidimensional scaling (NMDS) was used to determine clustering patterns of the samples, and correlative methods were used to determine which OTUs were significantly associated with the movements of samples along the NMDS axes. The presence of Saccharofermentans characterized the position of early samples, whereas the presence of Ruminococcus and Succiniclasticum were more indicative of the positions of later samples. Hydrogen accumulation and low sequence counts indicated low methanogen activity. Although both reactor systems were closed to microbial inputs due to the sterilization of influent media, we recorded significant increases in reactor diversity over time. This suggests that changes in the abundances of dominant community members may affect the sequencing of rare taxa within samples.

59 BASIC BIOLOGICAL SCIENCES↗

Early growth response 2 (EGR2) is a novel regulator of the senescence programme

Abstract Senescence, a state of stable growth arrest, plays an important role in ageing and age‐related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up‐regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down‐regulates p16 levels and increases the pool of p16− p21− ‘reversed’ cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence.

60 APPLIED LIFE SCIENCES↗

Poster — Thur Eve — 69: Computational Study of DVH-guided Cancer Treatment Planning Optimization Methods

Purpose: To compare methods to incorporate the Dose Volume Histogram (DVH) curves into the treatment planning optimization. Method: The performance of three methods, namely, the conventional Mixed Integer Programming (MIP) model, a convex moment-based constrained optimization approach, and an unconstrained convex moment-based penalty approach, is compared using anonymized data of a prostate cancer patient. Three plans we generated using the corresponding optimization models. Four Organs at Risk (OARs) and one Tumor were involved in the treatment planning. The OARs and Tumor were discretized into total of 50,221 voxels. The number of beamlets was 943. We used commercially available optimization software Gurobi and Matlab to solve the models. Plan comparison was done by recording the model runtime followed by visual inspection of the resulting dose volume histograms. Conclusion: We demonstrate the effectiveness of the moment-based approaches to replicate the set of prescribed DVH curves. The unconstrained convex moment-based penalty approach is concluded to have the greatest potential to reduce the computational effort and holds a promise of substantial computational speed up.

60 APPLIED LIFE SCIENCES↗

Methods and apparatus for multi-resolution replication of files in a parallel computing system using semantic information

Techniques are provided for storing files in a parallel computing system using different resolutions. A method is provided for storing at least one file generated by a distributed application in a parallel computing system. The file comprises one or more of a complete file and a sub-file. The method comprises the steps of obtaining semantic information related to the file; generating a plurality of replicas of the file with different resolutions based on the semantic information; and storing the file and the plurality of replicas of the file in one or more storage nodes of the parallel computing system. The different resolutions comprise, for example, a variable number of bits and/or a different sub-set of data elements from the file. A plurality of the sub-files can be merged to reproduce the file.

97 MATHEMATICS AND COMPUTING↗

Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain

Abstract We lack the fundamental information needed to understand how DNA damage in the brain is generated and how it is controlled over a lifetime in the absence of replication check points. To address these questions, here, we integrate cell-type and region-specific features of DNA repair activity in the normal brain. The brain has the same repair proteins as other tissues, but normal, canonical repair activity is unequal and is characterized by high base excision repair (BER) and low double strand break repair (DSBR). The natural imbalance creates conditions where single strand breaks (SSBs) can convert to double strand breaks (DSBs) and reversibly switch between states in response to oxidation both in vivo and in vitro. Our data suggest that, in a normal background of repair, SSBs and DSBs are in an equilibrium which is pushed or pulled by metabolic state. Interconversion of SSB to DSBs provides a physiological check point, which would allow the formation of unrepaired DSBs for productive functions, but would also restrict them from exceeding tolerable limits.

Science & Technology - Other Topics↗

Development of Laboratory Testbeds Simulating Real-World Greenhouse Gas Emissions

Climate change leads to drastic variations in the environment that can threaten food security. To protect the security and prosperity of the environment, new agricultural practices that mitigate greenhouse gas emissions need to be developed. Agriculture plays a large role in the emissions of greenhouse gases, thus a need for new practices. At present, testing landscape management practices for carbon sequestration and reduction of greenhouse gas emissions are expensive because such tests often require intricate field experiments. Laboratory tests on landscape management practices often fail to simulate and accurately represent the natural systems researchers intend to study. There are methods that can be used to make these laboratory tests more closely replicate natural systems for the improvement of agricultural lands used in biofuel and food production. The goal of this project is to develop a laboratory testbed replicating field conditions that will mimic field greenhouse gas emissions. To achieve this goal, we used soil cores taken from agricultural and marginal lands, then attached fiberglass wicks to improve the drainage system in the soil core to simulate a more natural hydraulic system. The soil cores with the wicks were used to compared to greenhouse gas emissions observed in the field. Our preliminary results suggest that the soil carbon dioxide and nitrous oxide flux from the agricultural land site were comparable to the soil cores equipped with the drainage wicks. The data suggests that laboratory testbeds can be used to mimic field greenhouse gas emissions if parameters, such as soil water content were in a set range. The laboratory testbed produces similar greenhouse gas emissions to the agricultural site when the soil water content was between 15-25%.

54 ENVIRONMENTAL SCIENCES↗

Using Eye Tracking to Elucidate the Mechanisms Underlying Stimulation-Enhanced Visual Target Detection

Transcranial direct current stimulation (tDCS) is a noninvasive form of brain stimulation that involves passing a weak electrical current between electrodes on the scalp to modulate underlying neural tissue. TDCS has been shown to modulate cognition in a variety of domains, including memory, attention, and visual processing. Prior work from our laboratory has shown positive effects of tDCS on learning to detect target objects hidden in complex naturalistic visual scenes and learn rules for categorizing images, though the mechanism for these benefits remains unknown. One possibility is that tDCS optimizes visual search by modulating visual attention or via the reduction in search errors. One method of quantifying visual attention is to use eye tracking to record search patterns to determine if and how visual search is adjusted under verum stimulation conditions. Eye tracking data allows classification of errors into error types, including sampling errors (failing to look in the relevant region), recognition errors (looking at the critical portion of a scene, but failing to recognize it as such as evidenced by visual fixation), and decision-making errors (fixating on the relevant portion of a scene, but making the wrong determination). Our results indicate that the benefit tDCS confers on visual search for targets stems from the reduction in decision-making errors when targets are present (Cohen’s d = 0.86). Also reported is a replication of previous findings showing a tDCS-dependent improvement in learning this task, learning score (Cohen’s d = 0.88); d’ (Cohen’s d = 1.00). This provides support for moving tDCS into the application space by pairing it with analysts who are concerned with the type of search error that is corrected via stimulation.

attention↗

Investigating YAP’s role in Human Mammary Epithelial Cell (HMEC) Immortalization and Cancer Stem Cell (CSC) Phenotype Acquisition during Early Breast Cancer Progression

The malignant aspect of tumorigenesis in breast cancer is initiated when human mammary epithelial cells (HMEC) first immortalize (gain the ability to proliferate indefinitely) and subsequently undergo oncogenic activation. Our laboratory has developed a two-step HMEC immortalization process that we believe accurately models early breast cancer progression. Normal finite pre-stasis HMEC must overcome two distinct senescence barriers to achieve full immortality: stasis (stress-associated senescence) and replicative senescence, respectively. HMEC bypass stasis, and become post-stasis, when errors in the retinoblastoma pathway are present. Replicative senescence, a product of continuously shortening telomeres producing telomere dysfunction, is overcome by the reactivation of telomerase. Our lab has called HMEC that acquire the error allowing telomerase expression conditionally immortal (CI); CI cells may still have low telomerase expression. Full immortality is achieved when sufficient telomerase expression exists to maintain short stable telomeres following a process we have called conversion. The transcriptional coactivator YAP, upregulated in several human cancers, is closely correlated with a variety of oncogenic effects including proliferation and induction of cancer stem cell (CSC) properties. Our preliminary data have shown that YAP-transduced post-stasis HMEC expressed properties of CI cells. Growth curves indicated that some cell lines achieved full immortality; however, these cells had acquired an additional error – amplified expression of c-Myc, an oncogene known to induce telomerase in post-stasis or CI cells. The absence of uniform immortalization in the YAP-transduced cells suggests that YAP causes post-stasis HMEC to become conditionally immortal. This is further supported given that YAP-transduced post-stasis HMEC have decreased levels of the lncRNA MORT and rapidly go through conversion when p53 function is abrogated, well-documented attributes of CI HMEC. Previous studies have also reported that YAP controls the differentiation of breast progenitor cells; as a result, it is likely that YAP plays a role in inducing CSC phenotypes. In this study, we attempt to gain a greater understanding of YAP’s role in HMEC immortalization and induction of CSC properties in early breast cancer progression. We measured gene expression levels and attempted to identify proteins indicative of a CSC phenotype in YAP-transduced post-stasis HMEC. Our initial results did not reveal an association between YAP and HMEC conditional immortality or induction of CSC attributes in the cultures examined. However, using a YAP construct that promotes nuclear localization (where YAP is most active) has led to a potentially promising YAP-derived cell line that we presume to be immortal. We go on to demonstrate that YAP may be acting via non-transcriptional oncogenic roles in our HMEC specimens. Thus, we recommend future studies into YAP and the HMEC immortalization process given that they are promising targets for breast cancer prevention therapies.

Shah, Manav↗

Machine Learning for Automated Extraction of Building Geometry

As data science comes to buildings, the promise of using machine learning and novel sources of data has received much attention. Advances in machine learning and computer vision algorithms, combined with increased access to unstructured data (e.g., images and text), have created an opportunity for automated extraction of building characteristics – cost-effectively, and at scale. Acquisition of features such as footprint are time consuming and costly to acquire with today’s manual methods, but can be streamlined through intelligent software-based solutions applied to satellite images. When combined with aerial RGB and thermal images, full 3D geometries and thermal maps can be constructed to determine additional characteristics such as window to wall ratio, height, number of stories and envelope thermal characteristics. In this paper we present three contributions to accelerate these high potential opportunities: (1) a methodical analysis of how these features can be integrated into today’s simulation and data driven software tools to enhance efficiency measure identification and owner/operator decision making; (2) development and accuracy testing of open source deep neural network methods to extract building footprints from satellite imagery, including the curation and application of openly available GIS datasets for training and continued development by others; and (3) an open framework for drone-based image capture and creation of 3D building geometries. This work represents an important bridge between high-level studies that span diverse application areas and those that detail point solutions yet cannot be easily replicated or extended.

Touzani, Samir↗

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ’omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. We report this work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.

59 BASIC BIOLOGICAL SCIENCES↗

TeMPI Shim

This is the manual for the TeMPI Shim library, whose goal is to facilitate scientific apps being loosely coupled through MPI. TeMPI Shim can be used to create and manage Message Passing Interface (MPI, see [MPI]) Communicators for Single Program, Multiple Data (SPMD, see [SPMD]) and Multiple Programs, Multiple Data (MPMD, see [MPMD]) workflows. MPI provides the MPI_APPNUM command number to each of the processes within its context. This number, starting at 0, is the application number being executed. In a case where 3 applications are being run in MPMD mode, there would be MPI_APPNUM values of 0, 1, and 2. TeMPI Shim creates intra- and inter-communicators between each pair of MPI_APPNUM values. In the aforementioned case, application 0 would have intra- and inter-communicators to speak to itself, application 1, and application 2. This is replicated for each of the applications. Additionally, TeMPI Shim creates intra- and inter-communicators for the first MPI rank of each application to directly communicate only with each other. Finally, TeMPI Shim creates its own copy of the default world communicator, i.e., MPI_COMM_WORLD. In the case where there is only a single application, it will have the communicators to only speak with itself. TeMPI Shim is useful in this case since it is considered good practice for MPI applications to copy the default world communicator and reference this copy (see [Duplicate World]_) anyways. Ultimately, it provides value independent of the number of applications present.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

SJL bone marrow-derived macrophages do not have IRF3 mutations and are highly susceptible to Theiler's virus infection

It is well known that SJL mice are susceptible to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease while C57BL6 (B6) and B10 mice are resistant, and H-2{sup s} on a B10 background (B10.S) contributes modestly to susceptibility. A recent study linked two IRF3 non-conservative mutations in SJL compared to B10.S mice to resistance to TMEV infection of SJL peritoneal-derived macrophages, an observation of practical interest in light of the central role of IRF3 transcription factor in the type I interferon (IFN) response. However, we did not find these non-conservative mutations among SJL, B10.S, B6 and B10 mice in the IRF3 amino acid sequence, and show SJL bone marrow-derived macrophages infected with TMEV exhibit increased virus RNA replication and infectious virus yields as well as greater IL-6 production than C57Bl strain (including B10.S) cultures. - Highlights: • We confirmed that Theiler's murine encephalomyelitis virus (TMEV)-infection in bone marrow-derived macrophages is significantly greater in susceptible SJL macrophages than in resistant C57BL macrophages. • We failed to confirm two non-conservative amino acid changes in IRF3 identified previously in SJL mice or differences in IRF3 activation after infection between the two mouse strain. However, IL-6 levels were significantly greater in infected SJL macrophages late in the infectious cycle. • The data also suggest that addition of the cytokine IL-6 to infected macrophage cultures is modestly antiviral.

60 APPLIED LIFE SCIENCES↗

Characterization of NORM in an Urban Environment using HPGe Measurements and MCNP6 Simulations

This work is part of a larger project aimed at producing an operationally relevant, validated simulation environment that can be used as a 'virtual testbed' for counterterrorism and counterproliferation efforts. Examples of such efforts include searches for illicit radiation sources before and during large special events, such as the presidential nominating conventions, inaugurations, and large sporting events. Once validated by laboratory and field measurements, this testbed can be used to test and validate algorithms and detector systems designed for various search missions in an urban environment. The detection of radioactive sources in a city is greatly complicated by natural background radiation, which emanates from various materials common to an urban environment, such as roadways, sidewalks, and building exteriors. The methods and results offered here represent the conclusion of an effort to characterize the concentration of naturally occurring radioactive material (NORM) in various elements in a controlled, but representative, urban environment. Some of the methods discussed in previous work will be briefly reiterated here, but more detail can be found in the preceding work. The location chosen for this effort was a Military Operations on Urban Terrain (MOUT) environment at the Fort Indiantown Gap (FTIG) National Guard training facility in Pennsylvania. This site was chosen because it replicates a small town where traffic and pedestrian access could be easily controlled, as to not interfere with the background measurements. This endeavor involved over 70 measurements using a high-purity germanium (HPGe) detector designed to ascertain the NORM concentrations in the soil, asphalt roads, gravel lots, concrete intersections, sidewalks, foundations, and walls found throughout the site. The NORM concentrations determined from this work will be incorporated into a large-scale simulation that can be used to investigate various search techniques and algorithms, detector types and setups, and to produce representative synthetic data for future work.

07 ISOTOPE AND RADIATION SOURCES↗

Introduction: Neuromorphic Materials

The explosive growth in data collection and the need to process it efficiently, as well as the desire to automate increasingly complex tasks in transportation, medical care, manufacturing, security and many other fields have motivated a growing interest in neuromorphic computing. Unlike the binary, transistorbased ON/OFF logic gates and separate logic and memory functionalities employed in digital computing, neuromorphic computing is inspired by animal brains that use interconnected synapses and neurons to perform processing, storage and transmission of information at the same location, while only consuming ~20 W or less of power. Motivated by the brain’s efficiency, adaptability, self-learning and resiliency qualities, neuromorphic computing can be broadly defined as an approach to processing and storing information using hardware and algorithms inspired by models of biological neural systems. Present research in neuromorphic computing encompasses approaches that vary significantly in their degree of neuro-inspiration, from systems that only incorporate features such as asynchronous, event-driven operation or use crossbar arrays of non-volatile memory (NVM) elements to accelerate deep neural networks (DNNs), to designs that embrace the extreme parallelism, sparsity, reconfigurability, adaptability, complexity and stochasticity observed in nervous systems. The term ‘neuromorphic’ computing is often credited to Carver Mead, who in the 1980s investigated Si-based analog electronics to replicate functions of the animal retina. Earlier important advances in this field include the work of Frank Rosenblatt, who proposed the concept of the perceptron, Bernard Widrow, who used this concept to build one of the first analog neural networks, the Adaline and many other researchers (see ref. 6 for an historical perspective on neuromorphic computing). With the recent increase in the use of artificial intelligence and large language models, and rising concerns over the associated energy costs, interest in neuromorphic hardware has expanded rapidly. According to some estimates, driven largely by the drastic growth in the training use of artificial intelligence (AI) models using the current computing architectures, the energy cost of computing is projected to reach the energy supply worldwide by 2045. Furthermore, while this is not a realistic outcome, it means that, if more efficient computing technologies are not developed -- soon -- the world will soon become one where demand for energy and market constraints limit the continued increase of societal access to AI and cloud services from data centers. Data centers used for training and use of these models consume hundreds of terawatt hours of electricity, already past 4% of the US electricity demand.

Circuits↗