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At least 289 records · Page 16

Scalability Testing Approach for Internet of Things for Manufacturing SQL and NoSQL Database Latency and Throughput

The proliferation of low-cost sensors and industrial data solutions has continued to push the frontier of manufacturing technology. Machine learning and other advanced statistical techniques stand to provide tremendous advantages in production capabilities, optimization, monitoring, and efficiency. The tremendous volume of data gathered continues to grow, and the methods for storing the data are critical underpinnings for advancing manufacturing technology. This work aims to investigate the ramifications and design tradeoffs within a decoupled architecture of two prominent database management systems (DBMS): sql and NoSQL. A representative comparison is carried out with Amazon Web Services (AWS) DynamoDB and AWS Aurora MySQL. The technologies and accompanying design constraints are investigated, and a side-by-side comparison is carried out through high-fidelity industrial data simulated load tests using metrics from a major US manufacturer. The results support the use of simulated client load testing for comparing the latency of database management systems as a system scales up from the prototype stage into production. As a result of complex query support, MySQL is favored for higher-order insights, while NoSQL can reduce system latency for known access patterns at the expense of integrated query flexibility. Here, by reviewing this work, a manufacturer can observe that the use of high-fidelity load testing can reveal tradeoffs in IoTfM write/ingestion performance in terms of latency that are not observable through prototype-scale testing of commercially available cloud DB solutions.

AWS↗

Structural analysis of the PTEN:P-Rex2 signaling complex reveals how cancer-associated mutations coordinate to hyperactivate Rac1

The dual-specificity phosphatase PTEN functions as a tumor suppressor by hydrolyzing PI(3,4,5)P 3 to PI(4,5)P 2 to inhibit PI3K-AKT signaling and cellular proliferation. P-Rex2 is a guanine nucleotide exchange factor for Rho GTPases and can be activated by Gβγ subunits downstream of G protein–coupled receptor signaling and by PI(3,4,5)P 3 downstream of receptor tyrosine kinases. The PTEN:P-Rex2 complex is a commonly mutated signaling node in metastatic cancer. Assembly of the PTEN:P-Rex2 complex inhibits the activity of both proteins, and its dysregulation can drive PI3K-AKT signaling and cellular proliferation. Here, using cross-linking mass spectrometry and functional studies, we gained mechanistic insights into PTEN:P-Rex2 complex assembly and coinhibition. We found that PTEN was anchored to P-Rex2 by interactions between the PDZ-interacting motif in the PTEN C-terminal tail and the second PDZ domain of P-Rex2. This interaction bridged PTEN across the P-Rex2 surface, preventing PI(3,4,5)P 3 hydrolysis. Conversely, PTEN both allosterically promoted an autoinhibited conformation of P-Rex2 and blocked its binding to Gβγ. In addition, we observed that the PTEN-deactivating mutations and P-Rex2 truncations combined to drive Rac1 activation to a greater extent than did either single variant alone. These insights enabled us to propose a class of gain-of-function, cancer-associated mutations within the PTEN:P-Rex2 interface that uncouple PTEN from the inhibition of Rac1 signaling.

D’Andrea, Laura↗

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Abstract Background Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. Methods We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. Results We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations inTP53,PLXNB3, Zinc finger genes, and fewer mutations inSDC2,CDH1,PIK3CA,SVIL, andPTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, includingKIAA1522,DCK,FOXO3,MYO9B,ARID1A,EPRS,ZC3HAV1, andRBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. Conclusions This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

Oncology↗

Adjoint sensitivity analysis and data assimilation for verification of dry storage cask contents

Dry cask storage is a method for interim storage of spent fuel assemblies which contain fissile isotopes of uranium and plutonium. These can present a proliferation concern and consequently there is a need for non-destructive testing methods to verify a dry cask's contents for proliferation protection. We present an application of adjoint sensitivity analysis and data assimilation to a multigroup diffusion model of dry cask storage. Adjoint sensitivity analysis allows the efficient calculation of sensitivities for use in data assimilation to calibrate imprecisely known parameter values and data consistency tests to detect diversion scenarios. (authors)

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

The Helix-Loop-Helix motif of human EIF3A regulates translation of proliferative cellular mRNAs

Improper regulation of translation initiation, a vital checkpoint of protein synthesis in the cell, has been linked to a number of cancers. Overexpression of protein subunits of eukaryotic translation initiation factor 3 (eIF3) is associated with increased translation of mRNAs involved in cell proliferation. In addition to playing a major role in general translation initiation by serving as a scaffold for the assembly of translation initiation complexes, eIF3 regulates translation of specific cellular mRNAs and viral RNAs. Mutations in the N-terminal Helix-Loop-Helix (HLH) RNA-binding motif of the EIF3A subunit interfere with Hepatitis C Virus Internal Ribosome Entry Site (IRES) mediated translation initiation in vitro . Here we show that the EIF3A HLH motif controls translation of a small set of cellular transcripts enriched in oncogenic mRNAs, including MYC . We demonstrate that the HLH motif of EIF3A acts specifically on the 5' UTR of MYC mRNA and modulates the function of EIF4A1 on select transcripts during translation initiation. In Ramos lymphoma cell lines, which are dependent on MYC overexpression, mutations in the HLH motif greatly reduce MYC expression, impede proliferation and sensitize cells to anti-cancer compounds. These results reveal the potential of the EIF3A HLH motif in eIF3 as a promising chemotherapeutic target.

59 BASIC BIOLOGICAL SCIENCES↗

Innovations in Sensors and Controls for Building Energy Management: Research and Development Opportunities Report for Emerging Technologies

Sensors, actuators, and controllers, which collectively serve as the backbone of cyberphysical systems for building energy management, are one of the core technical areas of investment for achieving the U.S. Department of Energy (DOE) Building Technologies Office's (BTO's) goals for energy affordability in the national building stock - both commercial and residential. In fact, an aggregated annual energy savings of 29% is estimated in the commercial sector alone through the implementation of efficiency measures using current state-of-the-art sensors and controls to retune buildings by optimizing programmable settings based on occupant schedules and comfort requirements, as well as detecting and diagnosing equipment operation and installation problems (Fernandez et al. 2017). Monitoring and control of building conditions and operations has advanced significantly, from the invention of the modern thermostat just before the start of the 20th century to the midcentury incorporation of direct digital control into devices, the introduction of open protocols and network communications at the end of the century, and finally the invention of cloud-based computing and additional advancements that have enabled remote operation and a proliferation of connected and intelligent devices in building automation. Despite this potential, however, two main challenges hinder widespread adoption of sensors and controls in building operations that can ensure savings for high-efficiency components and equipment (e.g., heat pumps, windows, and lighting devices), as well as additional savings from more sophisticated control architectures and algorithms. energy savings of 29% is estimated in the commercial sector alone through the implementation of efficiency measures using current state-of-the-art sensors and controls to retune buildings by optimizing programmable settings based on occupant schedules and comfort requirements, as well as detecting and diagnosing equipment operation and installation problems (Fernandez et al. 2017). Monitoring and control of building conditions and operations has advanced significantly, from the invention of the modern thermostat just before the start of the 20th century to the midcentury incorporation of direct digital control into devices, the introduction of open protocols and network communications at the end of the century, and finally the invention of cloud-based computing and additional advancements that have enabled remote operation and a proliferation of connected and intelligent devices in building automation. Despite this potential, however, two main challenges hinder widespread adoption of sensors and controls in building operations that can ensure savings for high-efficiency components and equipment (e.g., heat pumps, windows, and lighting devices), as well as additional savings from more sophisticated control architectures and algorithms.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

MITR Low-Enriched Uranium Conversion Fluid-Structure Interaction Preliminary Design Verification

The U.S. National Nuclear Security Administration (NNSA) Office of Material Management and Minimization (M 3 ) has developed and is pursuing an integrated approach to address the persistent threat posed by unintentional proliferation of nuclear materials. The NNSA M 3 approach reduces the risk of highly enriched uranium (HEU) and plutonium falling into the hands of non-state actors by minimizing the use of and, when possible, eliminating weapons-usable nuclear material around the world. In this geopolitical context, most research and test reactors, both domestic and international, have completed or started a program of conversion from the use of HEU to low-enriched uranium (LEU) as fuel. Conversion of civilian research reactors from HEU to LEU, and the return of the HEU to the country of origin, are important components of the NNSA non-proliferation program. Worldwide, 71 reactors have been converted to the use of LEU fuel, and an additional 32 have been confirmed to be permanently shut down. The U.S., with 20 reactor conversions, is among the 39 countries on six continents where conversions have occurred. With recent conversions in Ghana and Nigeria, an important milestone was reached in completing conversion of all reactors on the continent of Africa to LEU fuel. Africa thus becomes the third continent to have completed conversion of all HEU reactors to LEU, following Australia and South America

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

The Global Nonproliferation Regime: The NPT and Beyond

In the aftermath of WWII, the fear of nuclear war prompted the international community to confront the issue of nuclear proliferation. The global nonproliferation regime that exists today is comprised of a matrix of multilateral treaties, political commitments, and unilateral measures designed to limit the spread of nuclear weapons. It has evolved considerably since the dawn of the nuclear age. This presentation covers the origins of the Nuclear Non-Proliferation Treaty (NPT), an introduction to International Atomic Energy Agency (IAEA) safeguards, a discussion of contemporary challenges and opportunities in the field, and an overview of the broader nonproliferation regime beyond the NPT.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗

Radiation Detection Technologies

When governing bodies seek to reduce the spread and development of nuclear material and weapons, arms control and safeguards technologies play an important role in preventing proliferation within a state that has already developed a nuclear weapon. Arms control treaties work to control the development, production, stockpiling, proliferation, distribution, or the usage of a certain weapon type or delivery system. Treaty guidelines are met using combinations of monitoring, detection, and verification technologies. 1 To verify compliance, a country must determine if the activities of another country are within the limits and obligations established by the treaty. A verifiable treaty contains an interlocking web of constraints and provisions designed to deter cheating, to make cheating more complicated and more expensive, or to make its detection timelier. In the past, the U.S. has deemed treaties to be effectively verifiable if there is confidence that significant violations can be detected in time to respond and offset any threat that the violation may create for the U.S.

61 RADIATION PROTECTION AND DOSIMETRY↗

A Semi-Automated Approach for Curating a Glossary of Key Terms for Open-Source Data Queries

In FY20, the Savannah River National Laboratory (SRNL) was funded by the National Nuclear Security Administration’s Office of Defense Nuclear Non-Proliferation Research and Development (NA-22) to build a machine learning based modeling pipeline that could extract proliferation events of interest from open text-based data sources. As a test case, the research team targeted the identification/fusion of events and indicators that fissile core fabrication would be executed at the Savannah River Site prior to its official announcement in May of 2018. The demonstration prototype proved successful by applying natural language processing and graph theoretical techniques to identify contextual shifts in key words and phrases that acted as indicators that pit production would be carried out at the Savannah River Site up to two years prior to the official announcement.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Survey of U.S. Research Reactor Auxiliary Facilities Used for Material Testing and Basic Neutron Science

A catalogue of and attributes of the Materials Irradiation and Testing facilities (MIF) and the Basic Neutron Science facilities (BSF) of auxiliary (AUX) facilities of research reactors are compiled. The survey of these facilities is drawn from the set of U.S. university and DOE research reactor facilities and should be considered as a reference point when comparing commonalities in international AUX facilities. The size and shielding capabilities of the facilities, the typical characterization equipment used, and the neutron flux and irradiation capabilities of the facilities are listed. Short descriptions of experimental activities and current practices are detailed for MIFs and BSFs. The attributes are important in consideration of the reconfiguration of the facilities for purposes other than stated mission, i.e., for proliferation of weapons-usable nuclear material (WUNM). An evaluation of the capacity for production rate of WUNM from neutron beams-on-targets or a sample that has been placed in an irradiation position for a period is provided. Further evaluation of reconfiguration of these MIF and BSF are recommended to refine the proliferation risks. Specifically, MIF hot cells and potential configurations, additional modeling of facility throughput and development of methods for determining levels of concern for MIF and BSF have all been identified as steps for refinement of determination of the risks associated with these facilities. Future work will focus on: 1. A model of projected throughput for different MIF and BSF configurations that will be used to provide a window of potential operational misuse for a facility and better understand the capability of production and the rate of processing for WUNM in these facilities. 2. A misuse study for various configurations of MIF hot cell layouts detailing capacity, specifications, shielding constraints for MIF operations, identification of a maximum shielding thickness, and reasonable need associated with each activity performed in a MIF. 3. Development of a rule of thumb rating system utilizing data gathered from previous reports to show levels of concern at a given power level, flux, and experiment set.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Effect of Lateral Conduction in a Rectangular Fuel Plate and Optimum Stripe Widths for the OPAL Reactor

The impetus for this work is the Proliferation Resistance Optimization (PRO-X) program, which was created by the National Nuclear Security Administration (NNSA) of the US Department of Energy (DOE) to provide a framework for developing reactor designs that minimize the production of special nuclear materials while maximizing performance for peaceful uses. The Argentine company INVAP and Argonne National Laboratory collaborated to share knowledge and expertise regarding the thermal analysis of research reactors. Working together, they designed a series of test problems based on the Open Pool Australian Light Water (OPAL) reactor, whose fuel is in the form of flat plates cooled by water flowing through narrow rectangular channels. ANL used their PLTEMP/ANL code. INVAP used their TERMIC code (and its new multi-plate version, TERMIC-MP). Then, INVAP and ANL compared the two sets of results. 1-D models were used during the collaboration since for research reactor analysis, largely 1-D thermal-hydraulics models are commonly used because they are simple to apply and technically defendable. The collaboration between the two organizations aims for improvements in thermal-hydraulic models. Improvements to methods and models can reduce modeling uncertainties and excessive conservatism, allowing greater reactor performance without reducing predicted safety margins. Therefore, these improvements potentially expand the design space, making additional designs feasible, which, in turn, may achieve better fuel utilization and proliferation resistance in the designs. This report provides justification for the lateral node size (stripe width) chosen for the 1-D computer models during the collaboration. The lateral heat conduction in OPAL fuel plates is evaluated using the two-dimensional conduction capability of PLTEMP/ANL to determine a representative hot-stripe width that can be conservatively used for one-dimensional steady-state thermal-hydraulic analysis. Basically, a representative hot-stripe width needs to be selected so that the actual heat flux averaged over this stripe width is greater than or equal to the maximum heat flux obtained by the two-dimensional analysis. Detailed results in this report show that a hot-stripe width of 8.125 mm can be conservatively used for the one-dimensional thermal-hydraulics analysis of all plates. Therefore, eight equal stripes (8.125 mm each) are recommended to be modeled in the MCNP and PLTEMP/ANL full core models of the OPAL reactor.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

PRO-X Parallelization Study

The proliferation resistance optimization (PRO-X) program is actively supporting the design of nuclear systems by developing a framework to both optimize the fuel cycle infrastructure for nuclear reactor (including both advanced reactors (ARs) and research reactors (RRs)) and minimize the potential for production of weapons-usable nuclear material (Figure 1). One area of interest is in the impact a modular approach to bulk handling fuel cycle facilities could have on meeting safeguards requirements to identify future areas of growth within the proliferation resistance space. This study evaluates how changing the number of streams within a fuel cycle facility could impact a facilities ability to meet both domestic and international safeguards requirements.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Design of Hypothetical Processes for the Production of 131 I and 99 Mo from Activation Targets

For over six decades, medical isotope production has been a high-priority focus of many research reactors across the globe. The majority of these isotopes were produced using highly-enriched uranium (HEU) or low enriched uranium (LEU) – delivering millions of doses of diagnostic and therapeutic isotopes. As a consequence of this production, however, six decades of isotope production has resulted in massive quantities of spent uranium material worldwide with no known disposition pathway creating growing proliferation concerns. Supported by the National Nuclear Security Administration’s (NNSA) Material Management and Minimization (M3) program, there has been increased focus in the production of high-priority isotopes without special nuclear materials or without uranium altogether. Isotope production via activation can potentially fulfill regional isotope demands – particularly in under-developed regions without access to isotope supply chains. The benefits of this approach would be a reduction in uranium proliferation risks, less special nuclear material wastes, and reduced risk of supply disruption in the likely event that major isotope producers will again go off-line as has happened in recent years due to a number of factors.

07 ISOTOPE AND RADIATION SOURCES↗

Survey of emerging nuclear data needs for nonproliferation applications with advanced reactors

Nuclear science plays a key role in non-proliferation activities supporting advanced reactor technologies. Nuclear data underpin predictions and interpretations of nuclear material behavior and signatures in reactor fuel production, use, transport, and storage. Advanced reactors provide new challenges compared to the current fleet of thermal fission reactors. This report consolidates reported nuclear data needs from representative workshops, conferences, and publications, identifying six themes for recommended future investments supporting non-proliferation and safeguards applications. While also identified as data needs, major fission product evaluations and (α,n) reactions were omitted as there are ongoing activities producing new data under NA22/Objective O. Each theme is summarized below with example data and association with the nonproliferation mission for advanced fuels and reactors.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Synergistic effects of climate warming and atmospheric nutrient deposition on the alpine lake ecosystem in the south-eastern Tibetan Plateau during the Anthropocene

Alpine lakes on the Tibetan Plateau are highly sensitive to global change and have been recognized as the sentinel of climate warming. However, anthropogenic impacts in populated area are migrating to these remote areas via transporting particulate nutrients by atmospheric deposition. Whether warming and nutrient deposition would impose additive or synergistic effects on the lake ecosystem remains largely unknown. Here, we present multi-proxy (sediment pigment and geochemistry) records during the past two centuries at the Cuoqia Lake in the southeast Tibetan Plateau. We found that the lake exhibited rapid ecological changes since 1980 AD characterized by an increase in primary productivity due to algal proliferation, with more rapid growth of green algae and diatoms. These findings are in concert with many other lakes (e.g., Moon Lake and Shade Co) in the same area, suggesting a consistent pattern of ecosystem evolution at the region scale. Statistical analyses suggested that nutrient deposition and climate warming were strongly associated with the variations in primary productivity and algae composition, exerting both individual and interactive effects. In addition, scenario analyses with a well-established process-based ecosystem model further revealed that the two factors not only individually, but also synergistically promoted the algal proliferation and community succession. Such synergy is evident in that the effect of lake warming would be more pronounced under higher nutrient deposition scenario, which is potentially due to higher temperature-driven mineralization in warmer conditions, and higher efficiency of nutrient utilization under enhanced light availability attributing to declining ice thickness and duration in cold seasons. Overall, our study proposes the existence and quantifies the synergistic impacts of climate warming and anthropogenic activities in driving the ecological changes in remote alpine lakes on the Tibetan Plateau. The lake ecological consequences driven by individual factor would be worsen by such synergy, so that we cannot predict the lake ecosystem trajectory in the future based on each factor separately, and more efforts than previously expected would be needed for the lake restoration and management.

Zhang, Can↗

Bioenergy sorghum nodal root bud development: morphometric, transcriptomic and gene regulatory network analysis

Bioenergy sorghum’s large and deep nodal root system and associated microbiome enables uptake of water and nutrients from and deposition of soil organic carbon into soil profiles, key contributors to the crop’s resilience and sustainability. The goal of this study was to increase our understanding of bioenergy sorghum nodal root bud development. Sorghum nodal root bud initiation was first observed on the stem node of the 7 th phytomer below the shoot apex. Buds were initiated near the upper end of the stem node pulvinus on the side of the stem opposite the tiller bud, then additional buds were added over the next 6-8 days forming a ring of 10-15 nascent nodal root buds around the stem. Later in plant development, a second ring of nodal root buds began forming on the 17 th stem node immediately above the first ring of buds. Overall, nodal root bud development can take ~40 days from initiation to onset of nodal root outgrowth. Nodal root buds were initiated in close association with vascular bundles in the rind of the pulvinus. Stem tissue forming nascent nodal root buds expressed sorghum homologs of genes associated with root initiation (WOX4), auxin transport (LAX2, PIN4), meristem activation (NGAL2), and genes involved in cell proliferation. Expression of WOX11 and WOX5, genes involved in root stem niche formation, increased early in nodal root bud development followed by genes encoding PLTs, LBDs (LBD29), LRP1, SMB, RGF1 and root cap LEAs later in development. A nodal root bud gene regulatory network module expressed during nodal root bud initiation predicted connections linking PFA5, SPL9 and WOX4 to genes involved in hormone signaling, meristem activation, and cell proliferation. A network module expressed later in development predicted connections among SOMBRERO, a gene involved in root cap formation, and GATA19, BBM, LBD29 and RITF1/RGF1 signaling. Overall, this study provides a detailed description of bioenergy sorghum nodal root bud development and transcriptome information useful for understanding the regulation of sorghum nodal root bud formation and development.

09 BIOMASS FUELS↗

Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.

60 APPLIED LIFE SCIENCES↗