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At least 181 records · Page 10

The Pixel Anomaly Detection Tool : a user-friendly GUI for classifying detector frames using machine-learning approaches

Data collection at X-ray free electron lasers has particular experimental challenges, such as continuous sample delivery or the use of novel ultrafast high-dynamic-range gain-switching X-ray detectors. This can result in a multitude of data artefacts, which can be detrimental to accurately determining structure-factor amplitudes for serial crystallography or single-particle imaging experiments. Here, a new data-classification tool is reported that offers a variety of machine-learning algorithms to sort data trained either on manual data sorting by the user or by profile fitting the intensity distribution on the detector based on the experiment. This is integrated into an easy-to-use graphical user interface, specifically designed to support the detectors, file formats and software available at most X-ray free electron laser facilities. The highly modular design makes the tool easily expandable to comply with other X-ray sources and detectors, and the supervised learning approach enables even the novice user to sort data containing unwanted artefacts or perform routine data-analysis tasks such as hit finding during an experiment, without needing to write code.

47 OTHER INSTRUMENTATION↗

Continuous assessment of metabolic activity of mitochondria using resonance Raman microspectroscopy

Dysfunctional mitochondrial activity can lead to a variety of different diseases. As such, there exists a need to quantify changes in mitochondria function as it relates to these specific diseased states. Here, we present the use of resonance Raman (RR) spectroscopy as a tool to determine changes in isolated mitochondrial activity. RR spectroscopy, using 532 nm as the excitation source, specifically provides information on the reduction and oxidation (RedOx) state of cytochrome c, which is determined by the activity of protein complexes in the electron transport chain. In this model, injection of the substrate succinate into the mitochondrial sample is used to drive the electron transport chain, which causes a subsequent change in cytochrome c RedOx state. This change in RedOx state is tracked by RR spectroscopy. We report this tool gives real-time information on the rise and fall of the amount of reduced cytochrome c within the mitochondrial sample, providing a method for rapid assessment of mitochondrial metabolism that has broad applications in both basic science and medical research.

59 BASIC BIOLOGICAL SCIENCES↗

Improvements to the Flight Analysis and Simulation Tool (FAST) and Initial Development of the Genesis Flight Mechanics Simulation for Ascent, Aerocapture, Entry, Descent, and Landing (A2EDL) Trajectory Design

The NASA Engineering and Safety Center (NESC) was requested to provide significant enhancements to the Flight Analysis and Simulation Tool (FAST), a generic, variable-degree-of-freedom, multi-body ascent, aerocapture, entry, descent, and landing (A2EDL) flight simulation code and a key Agency analysis tool. This report details the upgrades to FAST that were completed, describes a change to the assessment’s scope that allowed its goals to be exceeded with a new and innovative approach, and discusses the results of the modified approach.

NASA Engineering and Safety Center; Flight Analysi↗

Reporting Differences Between Spacecraft Sequence Files

A suite of computer programs, called seq diff suite, reports differences between the products of other computer programs involved in the generation of sequences of commands for spacecraft. These products consist of files of several types: replacement sequence of events (RSOE), DSN keyword file [DKF (wherein DSN signifies Deep Space Network)], spacecraft activities sequence file (SASF), spacecraft sequence file (SSF), and station allocation file (SAF). These products can include line numbers, request identifications, and other pieces of information that are not relevant when generating command sequence products, though these fields can result in the appearance of many changes to the files, particularly when using the UNIX diff command to inspect file differences. The outputs of prior software tools for reporting differences between such products include differences in these non-relevant pieces of information. In contrast, seq diff suite removes the fields containing the irrelevant pieces of information before processing to extract differences, so that only relevant differences are reported. Thus, seq diff suite is especially useful for reporting changes between successive versions of the various products and in particular flagging difference in fields relevant to the sequence command generation and review process.

Khanampompan, Teerapat↗

Report on the Integration of Experimental and Modeling Data for Initial Equivalence Study of Mechanical Performance in Irradiated LPBF 316 Stainless Steel

To ensure the rapid development, deployment, and use of advanced nuclear technologies, faster qualification approaches are needed. Typically, the primary pathway uses traditional data packages consistent with the American Society of Mechanical Engineers Boiler and Pressure Vessel Code, which does not consider the environmental effects the material will experience such as corrosion and radiation damage. Examining radiation effects requires a significant amount of space in US facilities at the Advanced Test Reactor and the High Flux Isotope Reactor (HFIR) and suffers from natural gradients in temperature and neutron flux profiles. Ion irradiation may enable rapid assessment of radiation-induced damage to a material and is proposed as part of an accelerated materials qualification framework through the Advanced Materials and Manufacturing Technologies program. To enhance the utility of ion irradiation as an examination tool, this report provides the initial assessment of engineering-relevant properties of microstructures produced from ion irradiation in the near-surface volume. Nanoindentation, Vickers hardness, and known tensile properties were brought together with simple mathematical models and experimental data for an initial equivalence study of the mechanical performance of irradiated laser powder bed fusion (LPBF) 316 stainless steels across length scales. Direct observation of the calculated ion irradiation yield stress and measured neutron irradiation yield stress at 2 dpa showed that both datasets exhibit the same trend with irradiation temperature and overlap within an acceptable band of stress values. Ion irradiations at 10 dpa serve as a prediction of properties to compare to postirradiation examination of HFIR-irradiated LPBF 316H further in the program. This work is a significant demonstration of the Licensing Approach with Ions and Neutrons, which uses ion irradiations to generate mechanical property information more rapidly than through neutron irradiations.

36 MATERIALS SCIENCE↗

Investigating Application of LiDAR for Nuclear Power Plants

Many evaluation, assessment, and modeling tasks at nuclear power plants require spatial in-formation; this often requires physical visits to locations within the facility because the 2D or 3D schematics and current models do not contain enough detail or do not capture as-built and real-world conditions. These visits require extensive manual labor for not only the requesting party, but also support groups, such as security. Light Detection and Ranging (LiDAR) mapping is trying to solve that problem by providing very detailed 3D models for low costs. However, the use of these models can be very limited because either component reference information is missing and too costly to add or there is no way to extract specific spatial data needed for other tools. This report outlines two main efforts. First, to reduce the effort of “Tagging” data in large 3D models, a general Application Programming Interface (API) was developed to import a variety of existing plant database information into a 3D-visualization engine. Filters allow the user to have only zone-specific items listed; then, they can simply click and assign the information to a specific spot or component in the 3D model. The second part of the work is the development of an interface for importing pieces from the3D-LiDAR model into other systems needed for modeling and simulation, outlined around fire modeling. This interface allows for the retrieval of item location and boundaries, enabling the auto generation of models for varying tools.

3D Modelling↗

Industry Level Feasibility of LiDAR Data into Fire Modeling Using Fire Risk Investigation in 3D (FRI3D)

Many evaluation, assessment, and modeling tasks at nuclear power plants require spatial information this often requires physical visits to locations within the facility because the 2D or 3D schematics and current models do not contain enough detail or do not capture as-built and real-world conditions. These visits require extensive manual labor for not only the requesting party, but support groups such as security. LIDAR mapping is trying to solve that problem by providing very detailed 3D models for low costs. However, the use of these models can be very limited because either component reference information is missing and too costly to add, or there is no way to extract specific spatial data needed for other tools. This report presents Idaho National Lab's work with Environmental Intellect (Ei) covering two main efforts. First, to reduce the effort of "tagging" data in large 3D models. By using both existing plant database information, and artificial intelligence (AI) to find and read equipment labels. This research explores the ability of to provide a simple way for the user to tag items and verify plant data, capturing both the speed of AI and human verification. The second part of the work is the development of an interface for importing pieces needed for Modeling & Simulation. Analysis work such as that for fire, flood, or physical security all require spatial or 3D models in various levels of detail. This interface will allow for the retrieval of item location or boundaries, enabling the auto generation of models for varying tools. The application program interface (API) of the fire risk investigation in 3D (FRI3D) was used to test feasibility of exporting the LiDAR tagged spatial information. Outcomes from this work provide preliminary data to determine if the tools and methods could provide substantial industry benefit if fully matured.

97 MATHEMATICS AND COMPUTING↗

Nanobody-enabled monitoring of kappa opioid receptor states

Recent studies show that GPCRs rapidly interconvert between multiple states although our ability to interrogate, monitor and visualize them is limited by a relative lack of suitable tools. We previously reported two nanobodies (Nb39 and Nb6) that stabilize distinct ligand- and efficacy-delimited conformations of the kappa opioid receptor. Here, we demonstrate via X-ray crystallography a nanobody-targeted allosteric binding site by which Nb6 stabilizes a ligand-dependent inactive state. As Nb39 stabilizes an active-like state, we show how these two state-dependent nanobodies can provide real-time reporting of ligand stabilized states in cells in situ. Significantly, we demonstrate that chimeric GPCRs can be created with engineered nanobody binding sites to report ligand-stabilized states. Our results provide both insights regarding potential mechanisms for allosterically modulating KOR with nanobodies and a tool for reporting the real-time, in situ dynamic range of GPCR activity.

60 APPLIED LIFE SCIENCES↗

Tools for genetic engineering and gene expression control in Novosphingobium aromaticivorans and Rhodobacter sphaeroides

ABSTRACT Alphaproteobacteria have a variety of cellular and metabolic features that provide important insights into biological systems and enable biotechnologies. For example, some species are capable of converting plant biomass into valuable biofuels and bioproducts that have the potential to contribute to the sustainable bioeconomy. Among the Alphaproteobacteria, Novosphingobium aromaticivorans , Rhodobacter sphaeroides , and Zymomonas mobilis show promise as organisms that can be engineered to convert extracted plant lignin or sugars into bioproducts and biofuels. Genetic manipulation of these bacteria is needed to introduce engineered pathways and modulate expression of native genes with the goal of enhancing bioproduct output. Although recent work has expanded the genetic toolkit for Z. mobilis , N. aromaticivorans and R. sphaeroides still need facile, reliable approaches to deliver genetic payloads to the genome and to control gene expression. Here, we expand the platform of genetic tools for N. aromaticivorans and R. sphaeroides to address these issues. We demonstrate that Tn 7 transposition is an effective approach for introducing engineered DNA into the chromosome of N. aromaticivorans and R. sphaeroides . We screen a synthetic promoter library to identify isopropyl β-D-1-thiogalactopyranoside-inducible promoters with regulated activity in both organisms (up to ~15-fold induction in N. aromaticivorans and ~5-fold induction in R. sphaeroides ). Combining Tn 7 integration with promoters from our library, we establish CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference systems for N. aromaticivorans and R. sphaeroides (up to ~10-fold knockdown in N. aromaticivorans and R. sphaeroides ) that can target essential genes and modulate engineered pathways. We anticipate that these systems will greatly facilitate both genetic engineering and gene function discovery efforts in these species and other Alphaproteobacteria. IMPORTANCE It is important to increase our understanding of the microbial world to improve health, agriculture, the environment, and biotechnology. For example, building a sustainable bioeconomy depends on the efficient conversion of plant material to valuable biofuels and bioproducts by microbes. One limitation in this conversion process is that microbes with otherwise promising properties for conversion are challenging to genetically engineer. Here we report genetic tools for Novosphingobium aromaticivorans and Rhodobacter sphaeroides that add to the burgeoning set of tools available for genome engineering and gene expression in Alphaproteobacteria. Our approaches allow straightforward insertion of engineered pathways into the N. aromaticivorans or R. sphaeroides genome and control of gene expression by inducing genes with synthetic promoters or repressing genes using CRISPR interference. These tools can be used in future work to gain additional insight into these and other Alphaproteobacteria and to aid in optimizing yield of biofuels and bioproducts.

Hall, Ashley N.↗

Simple, Secure, Internet Delivery of MOOSE-based Applications

Application packaging and distribution are the final steps for delivering software to end-users; both are frequently neglected when creating scientific software. Commercial businesses rely on electronic distribution systems that have rendered disk drives obsolete. Still, national laboratories continue to rely heavily on removable media to distribute and limit access to controlled applications. With increasing concerns of unauthorized copying of sensitive applications, a modern distribution system that utilizes cryptographically secure communication and authentication protocols has been developed. This new distribution system will secure the chain of custody for nuclear software while simultaneously simplifying access to these tools. This report summarizes four primary advancements made toward the secure distribution of Nuclear Energy Advanced Modeling and Simulation (NEAMS)-developed, Multiphysics Object Oriented Simulation Environment (MOOSE)-based applications: application installation, package distribution, automated package building, and distribution of documentation. NEAMS is currently developing more than ten separate applications based on the open-source MOOSE Framework. Distribution of these applications has primarily been accomplished by distributing source code, with end-users compiling the applications themselves. This work created a mechanism where MOOSE applications can be installed in a similar way to any other software. This allows both administrators and end-users simplified access to runnable executables. With this new installation capability, it was then possible to rethink distribution. A new, secure capability for delivering MOOSE-based applications over the internet has been created. This system requires unique cryptographic tokens for authentication, greatly securing the custody chain for software. Once granted access, installation of any NEAMS code can be accomplished with these terminal commands: "conda install ncrc" "ncrc install ncrc-bison." After these two commands (and authenticating) the BISON application will be securely down- loaded from Idaho National Laboratory (INL)’s servers, installed, and ready to use. To enable this new distribution capability to be successful, the open-source Continuous Integration, Verification, Enhancement, and Testing (CIVET) Continuous Integration (CI) capability was augmented to add Continuous Delivery (CD). CD enables the automated building and packaging of MOOSE-based applications as they are modified by development teams, ensuring that our customers can obtain up-to-date versions of the software at any time. The need for instruction on how to use these applications was addressed through modifications to the MOOSE documentation system. The MooseDocs capability, which enables robust documentation of MOOSE-based applications, has been extended to allow both for the installation of documentation and the packaging of documentation with installed applications. Together, these enhancements form the core of a new, secure distribution mechanism for nuclear simulation tools. In concert with the Nuclear Computational Resource Center (NCRC), NEAMS- developed applications will now be straightforward to obtain securely.

97 MATHEMATICS AND COMPUTING↗

srlife: A Fast Tool for High Temperature Receiver Design and Analysis

This report describes a tool for estimating the structural service life of tubular, panel solar receivers operating at high temperatures. A complete version of the tool is available as open source software at https://github.com/Argonne-National-Laboratory/srlife and can be installed through the PyPi (https://pypi.org) package manager. Given the basic receiver geometry and the thermal loads on the receiver, the tool provides 1D, 2D, or 3D thermal and structural (single tube and simplified system) analysis and creep-fatigue service life prediction for six metallic alloys – 316H, 800H, Alloy 617, Alloy 740H, and Alloy 230. With the exception of Alloy 230 where the material data is preliminary, the software included a detailed set of models for the materials, well-supported by high temperature experimental test data. The tool is designed for easy integration with a software stack, including solar field and thermohydraulic simulations, for optimizing receiver designs to meet service life and economic targets. The report describes several heuristics that can be applied in srlife to reduce the analysis time by several orders of magnitude but with fairly accurate life estimation when compared with full analysis. The report provides several examples demonstrating the utility of srlife in receiver design. Finally, the report discusses high temperature tests on Alloy 282, collected as part of this project, used to develop and support the material model for that alloy.

47 OTHER INSTRUMENTATION↗

LncRNA cancer susceptibility candidate 15 accelerates the breast cancer cells progression via miR-153–3p/KLF5 positive feedback loop

Highlights: • CASC15 expression level was aberrantly high-expressed in breast cancer tissue specimens and cells. • Loss-of-functional experiments showed that knockdown of CASC15 suppressed the malignant behaviors of breast cancer cells. • CASC15 functioned as ceRNA of miR-153–3p, besides, miR-153–3p targeted the 3‘-UTR of KLF5 mRNA. • KLF5 binds with the promoter region of CASC15 and activates the transcription. Emerging literature have illustrated the vital regulatory roles of long noncoding RNAs (lncRNAs) on the breast cancer tumorigenesis. Although series of researches have been proceeded on the pathogenesis, there are still much of unsolved mysteries worth investigating. This study uncovered that CASC15 expression level was aberrantly high-expressed in breast cancer tissue specimens and cells. Functionally, the loss-of-functional experiments showed that knockdown of CASC15 suppressed the malignant behaviors of breast cancer cells, such as proliferation, invasion and tumor growth in vitro and vivo. Mechanically, we confirmed that CASC15 functioned as a competing endogenous RNA (ceRNA) of miR-153–3p, besides, miR-153–3p targeted the 3‘-UTR of KLF5 mRNA utilizing the bioinformatics online tools, luciferase reporter assay and RNA immunoprecipitation. Interestingly, we confirmed that the transcription factor KLF5 binds with the promoter region of CASC15 and activates the transcription. In conclusion, we validated the positive feedback loop of KLF5/CASC15/miR-153–3p/KLF5 in the acceleration of breast cancer malignant behaviors and tumorigenesis, suggesting the important biologic roles of CASC15 on the breast cancer tumorigenesis.

60 APPLIED LIFE SCIENCES↗

Structure-Guided Development of a Potent and Selective Non-covalent Active-Site Inhibitor of USP7

Deubiquitinating enzymes (DUBs) have garnered significant attention as drug targets in the last 5–10 years. The excitement stems in large part from the powerful ability of DUB inhibitors to promote degradation of oncogenic proteins, especially proteins that are challenging to directly target but which are stabilized by DUB family members. Highly optimized and well-characterized DUB inhibitors have thus become highly sought after tools. Most reported DUB inhibitors, however, are polypharmacological agents possessing weak (micromolar) potency toward their primary target, limiting their utility in target validation and mechanism studies. Due to a lack of high-resolution DUB∙small-molecule ligand complex structures, no structure-guided optimization efforts have been reported for a mammalian DUB. In this paper, we report a small-molecule∙ubiquitin-specific protease (USP) family DUB co-structure and rapid design of potent and selective inhibitors of USP7 guided by the structure. Interestingly, the compounds are non-covalent active-site inhibitors.

59 BASIC BIOLOGICAL SCIENCES↗

Integrating diagnostics and model-based optimization

Energy Management and Information Systems are a family of analytics technologies that include energy information systems, fault detection and diagnostics (FDD), and automated system optimization tools. Such systems have the potential to enable buildings to meet energy management goals of reducing total energy consumption and cost. Most current market offerings use data-driven and rule-based analytics. However, the use of physics-based models in the analytics offers potential improvements by providing an accurate estimation of outputs based on representation of the physical principles governing the building system behaviors. This also permits the use of design stage models to inform commissioning and operation. This paper describes the development and testing of a hybrid data-driven and physics model-based operational tool for energy efficiency in central cooling plants. The tool offers FDD functionality, setpoint optimization, and visualization of key performance parameters. It was demonstrated at a university campus in the mixed-humid ASHRAE Climate Zone 4A. Key performance metrics that were analyzed include plant electricity use reduction, plant model calibration, and system economics. Annual simulations indicate the tool can provide electricity savings of greater than 10% for approximately six months of the year, mainly during the winter season when wet bulb temperatures are low, though only 1.38% savings for the entire year. Additionally, over a 4-day period in April, recommended optimal setpoints were implemented, resulting in 17% savings versus metered baseline consumption. With respect to model calibration, the difference between model-predicted and measured parameters was less than 10% for 90% of data points acquired for three of six chillers, and for each ten cooling towers. Finally, the tool users reported that satisfaction with the capabilities was equal to or better than that with the preexisting BAS system.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After 131 I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma

We report few tools exist to predict clinical outcomes after radiopharmaceutical therapy. Our goal was to identify associations between blood-based biomarkers of radiation effect and clinical outcomes after 131 I-metaiodobenzylguanidine ( 131 I-MIBG) therapy in patients with neuroblastoma. We conducted a prospective, single-center cohort study in children with advanced neuroblastoma treated with 131 I-MIBG as monotherapy or in combination with systemic putative radiation sensitizers. We collected serial peripheral blood samples after 131 I-MIBG infusions and quantified a panel of protein and messenger RNA markers. We plotted relative change from baseline to assess degree of modulation over time and then evaluated association of marker modulation with toxicity and response endpoints. The cohort included 40 patients (30 male/10 female; median age 7 years). We observed significant modulation of the majority of markers between baseline and hour 72 after 131 I-MIBG. Greater fold increase of plasma FLT3 ligand was associated with subsequent grade 4 neutropenia (P=.039). Modulation of peripheral blood BCLXL and DDB2 was associated with grade 3+ nonhematologic toxicity (P=.043 and .048, respectively). No markers were associated with tumor response. Greater plasma FLT3 ligand, BCLXL, and BCL2 modulation was observed in patients receiving 131 I-MIBG in combination with radiation sensitizers. Among 9 patients who received 2 courses, the degree of modulation in serum amylase was significantly lower after the second course (P=.012). Peripheral blood biomarkers relevant to radiation exposure are significantly modulated during the acute period after 131 I-MIBG. The degree of modulation of a subset of these markers is associated with toxicity and receipt of concomitant radiation sensitizers.

131I-MIBG↗

A Markov chain Monte Carlo (MCMC) Bayesian inference approach to analyze apparent activation barriers and reaction orders from microreactor data

Statistical analysis of steady-state catalytic kinetic data is often limited by data sparsity due to the slow pace at which the data is collected. Data sparsity and limitations in statistical analysis make it difficult to differentiate between mechanistic models and catalytic sites. A Bayesian inference tool is reported for catalysis researchers to estimate error in the determination of reaction orders from steady state microreactor data. The benefits of a Bayesian inference approach are discussed, as an alternative to the more common frequentist approach. The approach incorporates prior knowledge of the system and the data collected to form an error estimate on reaction orders. We investigated the effects of three distinct data treatments—individual fitting of trials, pooled analysis, and constrained regression methods—on the precision and uncertainty of reaction order determinations. To assess the robustness of our findings, we conducted sensitivity analyses to evaluate the influence of Bayesian parameters on uncertainty estimation. Additionally, we utilized synthetic data to illustrate how data quality impacts the precision of uncertainty assessments. We show Bayesian analysis can obtain a more precise estimation of error with a sparse data set than a frequentist analysis. Finally, this work provides strong evidence that the adoption of Bayesian analysis of kinetic data may help researchers make more precise arguments as to the strength of their evidence for a particular mechanistic hypothesis, or in comparing across different catalysts.

42 ENGINEERING↗

Deconvolution of octahedral Pt 3 Ni nanoparticle growth pathway from in situ characterizations

Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning. Yet, it remains a challenge due to complexity of the growth process and technical limits of modern characterization tools. We report a combinational use of multiple cutting-edge in situ techniques to study the growth process of octahedral Pt3Ni nanoparticles, which reveal the particle growth and facet formation mechanisms. Our studies confirm the formation of octahedral Pt 3 Ni initiates from Pt nuclei generation, which is followed by continuous Pt reduction that simultaneously catalyzes Ni reduction, resulting in mixed alloy formation with moderate elemental segregation. Furthermore, carbon monoxide molecules serve as a facet formation modulator and induce Ni segregation to the surface, which inhibits the (111) facet growth and causes the particle shape to evolve from a spherical cluster to an octahedron as the (001) facet continues to grow.

36 MATERIALS SCIENCE↗

3D Optical Coherence Tomography image processing in BISCAP: characterization of biofilm structure and properties

Abstract Motivation BISCAP is a state-of-the-art tool for automatically characterizing biofilm images obtained from Optical Coherence Tomography. Limited availability of other software tools is reported in the field. BISCAP’s first version processes 2D images only. Processing 3D images is a problem of greater scientific relevance since it deals with the entire structure of biofilms instead of their 2D slices. Results Building on the image-processing principles and algorithms proposed earlier for 2D images, these were adapted to the 3D case, and a more general implementation of BISCAP was developed. The primary goal concerns the extension of the initial methodology to incorporate the depth axis in 3D images; multiple improvements were also made to boost computational performance. The calculation of structural properties and visual outputs was extended to offer new insights into the 3D structure of biofilms. BISCAP was tested using 3D images of biofilms with different morphologies, consistently delivering accurate characterizations of 3D structures in a few minutes using standard laptop machines. Low user dependency is required for image analysis. Availability and implementation BISCAP is available from https://github.com/diogonarciso/BISCAP. All images used in the tutorials and the validation examples are available from https://web.fe.up.pt/∼fgm/biscap3d.

Narciso, Diogo A. C. (ORCID:0000000227767477)↗