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At least 1,747 records · Page 97

Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles

Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) spike proteins that recognize SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles. Here, we describe neutralizing mAbs isolated from mosaic-8b-immunized rabbits, some on par with Pemgarda, the only currently FDA-approved therapeutic mAb. Deep mutational scanning, in vitro selection of spike resistance mutations, and single-particle cryo-electron microscopy structures of spike–antibody complexes demonstrated targeting of conserved RBD epitopes. Rabbit mAbs included critical D-gene segment RBD-recognizing features in common with human anti-RBD mAbs, despite rabbit genomes lacking an equivalent human D-gene segment, thus demonstrating that the immune systems of humans and other mammals can utilize different antibody gene segments to arrive at similar modes of antigen recognition. These results suggest that animal models can be used to elicit anti-RBD mAbs with similar properties to those raised in humans, which can then be humanized for therapeutic use, and that mosaic RBD nanoparticle immunization coupled with multiplexed screening represents an efficient way to generate and select broadly cross-reactive therapeutic pan-sarbecovirus and pan-SARS-CoV-2 variant mAbs.

Science & Technology - Other Topics↗

Structural basis for severe pain caused by mutations in the voltage sensors of sodium channel NaV1.7

Voltage-gated sodium channels in peripheral nerves conduct nociceptive signals from nerve endings to the spinal cord. Mutations in voltage-gated sodium channel NaV1.7 are responsible for a number of severe inherited pain syndromes, including inherited erythromelalgia (IEM). Here, we describe the negative shifts in the voltage dependence of activation in the bacterial sodium channel NaVAb as a result of the incorporation of four different IEM mutations in the voltage sensor, which recapitulate the gain-of-function effects observed with these mutations in human NaV1.7. Crystal structures of NaVAb with these IEM mutations revealed that a mutation in the S1 segment of the voltage sensor facilitated the outward movement of S4 gating charges by widening the pathway for gating charge translocation. In contrast, mutations in the S4 segments modified hydrophobic interactions with surrounding amino acid side chains or membrane phospholipids that would enhance the outward movement of the gating charges. These results provide key structural insights into the mechanisms by which these IEM mutations in the voltage sensors can facilitate outward movements of the gating charges in the S4 segment and cause hyperexcitability and severe pain in IEM. Our work gives new insights into IEM pathogenesis at the near-atomic level and provides a molecular model for mutation-specific therapy of this debilitating disease.

60 APPLIED LIFE SCIENCES↗

Machine learning for single-ended event reconstruction in PROSPECT experiment

The Precision Reactor Oscillation and Spectrum Experiment, PROSPECT, was a segmented antineutrino detector that successfully operated at the High Flux Isotope Reactor in Oak Ridge, TN, during its 2018 run. Despite challenges with photomultiplier tube base failures affecting some segments, innovative machine learning approaches were employed to perform position and energy reconstruction, and particle classification. This work highlights the effectiveness of convolutional neural networks and graph convolutional networks in enhancing data analysis. By leveraging these techniques, a 3.3% increase in effective statistics was achieved compared to traditional methods, showcasing their potential to improve analysis performance. Furthermore, these machine learning methodologies offer promising applications for other segmented particle detectors, underscoring their versatility and impact.

47 OTHER INSTRUMENTATION↗

Improving ICARUS track reconstruction algorithms

The ICARUS experiment is part of the Short-Baseline Neutrino program at Fermilab. Its primary objective is to explore the possible existence of sterile neutrinos in the O(1 eV) mass range and to clarify the anomalies observed in the Liquid Scintillator Neutrino Detector and MiniBooNE experiments. The ICARUS-T600 detector is a Liquid Argon Time Projection Chamber, capable of producing high-resolution 3D images and precise calorimetric measurements of ionizing particles. This technology allows for a detailed study of neutrino interactions across a broad energy range, from a few keV to several hundred GeV. The track reconstruction is achieved through a software framework that applies a series of pattern recognition algorithms, transforming raw detector signals into fully reconstructed event topologies. This process involves identifying interaction vertices, particle tracks, and electromagnetic showers within the TPC. However, in certain cases, these algorithms may mistakenly break a single particle track into several shorter segments, interpreting each as a distinct particle. Since track length is used to estimate the particle's energy, such fragmentation can result in an energy underestimation of several hundred MeV. Furthermore, when a track is split into multiple segments, the particle identification (which relies on analyzing the energy loss as a function of the residual range) may fail, potentially leading to the loss of the entire event. To mitigate this problem, we have developed a dedicated algorithm designed to identify and reconnect (“stitch”) the tracks that were erroneously divided into multiple segments.

Ricci, Alessandro Maria [Pisa U.; INFN, Pisa] (ORC↗

BCG alignment with the locations of cluster members and the large-scale structure out to 10 R 200

Using a sample of >200 clusters, each with typically 100–200 spectroscopically confirmed cluster members, we search for a signal of alignment between the position angle (PA) of the Brightest Cluster Galaxy (BCG) and the distribution of cluster members on the sky about the cluster centre out to projected distances of 3 R 200 . The deep spectroscopy, combined with corrections for spectroscopic incompleteness, makes our sample ideal to determine alignment signal strengths. We also use an SDSS based skeleton of the filamentary large-scale structure (LSS), and measure BCG alignment with the location of the LSS skeleton segments on the sky out to projected distances of 10 R 200 . The alignment signal is measured using three separate statistical measures; Rao’s spacing test (U), Kuiper’s V parameter (V), and the Binomial probability test (P). The significance of the BCG alignment signal with both cluster members and LSS segments is extremely high (1 in a million chance or less to be drawn randomly from a uniform distribution). We investigate a wide set of parameters that may influence the strength of the alignment signal. Clusters with more elliptical-shaped BCGs show stronger alignment with both their cluster members and LSS segments. Also, selecting clusters with closely connected filaments, or using a luminosity-weighted LSS skeleton, increases the alignment signal significantly. Alignment strength decreases with increasing projected distance. Combined, these results provide strong evidence for the growth of clusters and their BCGs by preferential feeding along the direction of the filaments in which they are embedded.

79 ASTRONOMY AND ASTROPHYSICS↗

DC-Ripple-Energy Adaptive-Minimization (DREAM) Modulation Scheme for a High Power Density Inverter

The DC bus capacitor is one of the major power-density and reliability hurdles of electric drive systems. It is hard to shrink because it is constrained by the DC bus RMS ripple current, which is only load dependent. A dual-inverter based segmented drive can reduce the ripple current by ~50% compared to a non-segmented case. This paper analyzes the origin of this ripple current and points out the path for minimization. An optimal DC-ripple-energy adaptive-minimization (DREAM) modulation method is proposed to further reduce the ripple current. It is observed in experimental results that the proposed method can achieve additional 38% reduction over the traditional segmented drive system.

Xue, Lincoln↗

A High-Speed High-Power-Density Non-Heavy Rare-Earth Permanent Magnet Traction Motor

There has been a global push for higher torque density and lower cost traction motors. The use of non-heavy rare-earth (non-HRE) permanent magnet materials in traction motors are being investigated for the sustainability, profitability and affordability of electric vehicles and to broaden their adoption. A 20,000-rpm permanent magnet traction motor using non-HRE magnet materials is proposed. A dual three-phase winding configuration driven by a segmented dual three-phase drive is proposed to reduce the current ripple, and as a result, the DC Link capacitor, as well as to ease the voltage constraint at high speed and eliminate any risk of uncontrolled regeneration. Furthermore, the dual winding configuration enables a fault tolerant design which is useful for reliability. The paper presents comprehensive electromagnetic, thermal and mechanical designs and analyses using an integrated approach. The results have shown that the design is robust against demagnetization and confirmed its thermal and mechanical viability.

47 OTHER INSTRUMENTATION↗

Real-time Implementation of Grid Code Compliant Grid Edge Energy Management System

Integrated distributed energy resources (DER) in a distribution system need to follow grid codes to avoid violations that result in DER/circuit segment disconnection. To comply with grid code requirements at the grid edge level, network constrained grid edge energy management system (EMS) can be deployed. The objective of grid edge EMS is to provide economic solution for active and reactive power DER setpoints at each dispatch interval and ensure voltage regulation to support secure interconnection of the grid edge segment to the distribution system with multiple inverter based DER units. In this work, real-time simulation of grid code compliant grid edge EMS is deployed in a realistic feeder circuit segment. For real-time simulation, communication between the grid edge EMS and DERs is done exploiting IEC 61850-7-420. It enables interoperability among different DERs and grid edge EMS. No prior art has deployed IEC 61850-7-420 GOOSE communication protocol for grid edge EMS. Conversion of IEC 61850 GOOSE messages to Modbus communication protocol is also performed to communicate with grid edge EMS in commodity-off the shelf embedded boards in this work. The real-time simulation in OPAL-RT real-time digital simulator shows the out-performance of grid edge EMS by reducing the voltage violation in the distribution circuit.

Energy management system↗

Ultrasonic Measurements of Temperature Distribution in Extreme Environments: Results of Power Plant Testing

The most hardened insertion sensors do not perform reliably in extreme environmental conditions. We address this problem by developing an ultrasonic thermometry system for the measurements of segmental temperature distributions (MSTD) in solid materials and, specifically, across containments of energy conversion processes. The MSTD approach uses an echogenically segmented ultrasound propagation path, structured to contain engineered or naturally occurring echogenic features. In pulse-echo mode, these features produce a train of echoes in response to an external pulse of ultrasonic excitation created and acquired by a transducer located outside the extreme environment. The delays between the echoes encode the information on the temperature distribution in the corresponding segments of the ultrasonic propagation path, which we use to reconstruct an unknown temperature profile. This note describes the preliminary results and initial experience in applying the developed MSTD ultrasonic thermometry system to the measurements of temperatures in a utility-scale 500MW coal-fired boiler.

John, Mason↗

Machine-Learning Architecture for Ultrasonic Thermometry

Temperature distribution in solids can be inverted from the speed of sound (SOS) measurements, as has been shown feasible by timing the propagation of the excitation pulse and the train of echoes in ultrasonically segmented waveguides (WGs) and metal components. However, complicated geometries and closely-space echogenic features (EFs) create complex waveforms, from which the segmental time of flights (TOFs) are impossible to estimate using traditional methods. This work describes a machine learning architecture shown to extract temperature information from complex ultrasonic waveforms without explicit measurements of segmental TOFs. We accomplish this by using an autoencoder neural network (NN) to map ultrasonic waveforms into a low-dimensional latent space. A second NN then maps the latent space into unknown temperature distribution along the WG. The proposed architecture was tested in simulations and experimentally. The autoencoder accurately reconstructs the waveforms from their latent representation, several orders of magnitude lower in dimensionality. The obtained latent space was successfully mapped into the temperature of the propagation path.

John, Mason↗

STRUCTURAL MODELING TO SUPPORT POST-YIELD ACCEPTANCE CRITERIA FOR SPENT NUCLEAR FUEL CLADDING

Spent nuclear fuel (SNF) is evaluated for structural failure during storage and transportation scenarios. The U.S. Department of Energy’s Spent Fuel and Waste Science and Technology (SFWST) program has sponsored significant research in quantifying mechanical loads on SNF during storage and transportation scenarios using experimental and modeling methods. The SFWST program has also performed significant research on measuring the mechanical behavior of irradiated SNF as defueled cladding segments and cladding with fuel pellets to measure composite behavior. This paper considers some of the key material data from the Sibling Pin testing and uses structural modeling and analysis methods that have been informed by testing to consider post-yield acceptance criteria for SNF cladding structural analysis. Test data published by Oak Ridge National Laboratory (ORNL) and Pacific Northwest National Laboratory (PNNL) are the foundation for informing the material behavior of the models developed in this study. In particular, four-point bend (4PB) tests of fueled and defueled cladding segments provide significant information about the bending failure mode of SNF. ORNL’s 4PB test data is on fueled cladding segments, so the composite behavior of SNF is demonstrated. This paper describes PNNL’s coincident beam model that was developed to approximate the composite behavior of SNF. This paper also presents PNNL’s structural dynamic finite element models of a cask tip-over scenario, which is predicted to cause the strongest mechanical loads on SNF of all postulated storage and transportation scenarios. SNF bending loads predicted in the cask tip-over scenario and cladding acceptance criteria beyond yield are considered, with justification based on the Sibling Pin test data. ASME Boiler and Pressure Vessel code stress intensity limits are also considered. The ultimate goal of this work is to aid in the justification of structural acceptance criteria for SNF cladding beyond the cladding’s irradiated yield strength for use in structural analysis of all storage and transportation scenarios.

Klymyshyn, Nicholas A.↗

Three-dimensional super line-localization in low signal-to-noise microscope images via prior-apprised unsupervised learning (PAUL)

Biological processes such as processive enzyme turnover and intracellular cargo tracking involve the dynamic motion of a small "article" along a curvilinear biopolymer track. To understand these processes that occur across multiple length and time scales, one must acquire both the trajectory of the particle and the position of the track along which it moves, possibly by combining high-resolution single-particle tracking with conventional microscopy. Yet, usually there is a significant resolution mismatch between these modalities: while the tracked particle is localized with a precision of 10 nm, the image of the surroundings is limited by optical difraction, with 200 nm lateral and 500 nm axial resolutions. Compared to the particle's trajectory, the surrounding curvilinear structure appears as a blurred and noisy image. This disparity in the spatial resolutions of the particle trajectory and the surrounding curvilinear structure image makes data reconstruction, as well as interpretation, particularly challenging. Analysis is further complicated when the curvilinear structures are oriented arbitrarily in 3D space. Here, we present a prior-apprised unsupervised learning (PAUL) approach to extract information from 3D images where the underlying features resemble a curved line such as a filament or microtubule. This three-stage framework starts with a Hessian-based feature enhancement, which is followed by feature registration, where local line segments are detected on repetitively sampled subimage tiles. In the final stage, statistical learning, segments are clustered based on their geometric relationships. Principal curves are then approximated from each segment group via statistical tools including principal component analysis, bootstrap and kernel transformation. This procedure is characterized on simulated images, where sub-voxel medium deviations from true curves have been achieved. The 3D PAUL approach has also been implemented for successful line localization in experimental 3D images of gold nanowires obtained using a multifocal microscope. Lastly, this work not only bridges the resolution gap between two microscopy modalities, but also allows us to conduct 3D super line-localization imaging experiments, without using super-resolution techniques.

42 ENGINEERING↗

Fracture length data for geothermal applications

Fracture lengths govern permeability and are unknowns in geothermal assessment. Along their lengths, fracture widths vary due to growth by linkage. Under the influence of diagenesis, narrow widths seal, breaking porosity continuity and reducing open length. The largest range of widths and thus susceptibility to fill occurs where fractures are linked by narrow segments. Outcrops of a geothermal target, Cambrian Potsdam quartz arenite, contain opening-mode fractures having lengths spanning five orders of magnitude from 0.082 mm to 17.9 m. Combined lengths measured at a range of scales can be described by power laws, but at a given image resolution, lengths are best fit by exponential functions. Owing to preferential sealing of small fractures, open fractures follow exponential functions, but values depend on rules for designating fractures as continuous. En échelon segments, offset 10 mm, are connected by narrow fractures or microfractures (hard linked) not evident on outcrop 1 m-elevation LiDAR or 30 m-height drone images. A rule that identifies where narrow and likely connected segments are located can yield lengths meaningful for flow simulation. Depending on diagenesis, continuity rules can halve or double average and maximum length values. Length values from outcrop for geothermal applications should be adjusted based on wellsite-specific diagenesis information.

15 GEOTHERMAL ENERGY↗

cabbi-bio/ESM-R-script

This script is intended to provide a starting point for users to implement the equivalent soil mass (ESM) approach for calculating soil organic carbon (SOC) stocks and SOC mass percentages (commonly called “SOC concentration”). The user should read this readme file and understand how the script works before using it. The script contains some basic error checking algorithms, but it cannot catch all data entry mistakes. It is possible to misuse the script and produce invalid results. The script was designed to work on individual soil cores that have been divided into three or more contiguous segments, as the cubic spline function contains four coefficients. The script has not been tested on soil cores containing fewer than three contiguous segments. If only one segment is present, interpolation will necessarily be linear rather than cubic, which is expected to result in higher predictive error (Wendt & Hauser, 2013). Considering the wide range of potential applications, the script should not be expected to function correctly in all situations. The user is encouraged to modify or rewrite the script to meet their specific needs.

von Haden, Adam↗

pnnl/defect_detection

The code takes expert-labeled segmented images of irradiated and unirradiated pellets and trains DeepConvolutional Neural Networks to segment these images into defects, backgrounds, and boundaries. The code calculated qualitative microstructural information from these segmented images to facilitate the comparison of unirradiated and irradiated pellets

Oostrom, Marjolein↗

Deep Neural Network Algorithm for CMC Microstructure Characterization and Variability Quantification

Microstructure characterization and variability quantification are crucial for understanding ceramic matrix composites (CMCs) mechanical behavior and deformation mechanisms across length scales. Traditionally, analyses of the micrographs obtained from microscopy are labor-intensive. However, with the vast improvement in computer vision (CV) and deep learning (DL), an automated algorithm can be designed to extract essential microstructure variability from micrographs which can then be used to construct a statistically representative volume element (SRVE). The DL-based algorithm spans the taxonomy of microstructure analyses, including semantic segmentation of microstructure constituents, secondary phases, matrix/fiber interface, and defects, and quantifying the microstructure variability in terms of probability distributions. In this work, C/SiNC and SiC/SiNC CMCs microstructures are semantically segmented through a deep convolutional neural network, followed by variability quantification through the implementation of a fully connected regression layer, hence forming a deep regression network. The deep regression network operates in a feedforward regime, in which the neuron output signal traverses through the network in a unidirectional manner. The weight tensor associated with each layer is updated through a backpropagation stochastic gradient descent approach. The input gray-scale image obtained through in-house scanning electron microscope and confocal microscope micrographs is augmented through affine transformations to increase the training set size, which is then processed through four strided convolutional layers. This compresses the image resolution by half at each layer while increasing the image depth by applying different filters (image encoding). The class activation maps (CAMs) corresponding to the applied filters highlight the key architectural features and assist with the semantic segmentation of the microstructure.

Hamza, Mohamed H.↗

Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that “run through” the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90 Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949–1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90 Sr and 89 Sr intake to humans.

59 BASIC BIOLOGICAL SCIENCES↗

Stochastic parametric skeletal dosimetry model for humans: Pediatric and adult computational skeleton phantoms for internal bone marrow dosimetry

Currently, computational phantoms that simulate skeletal tissues are used in active red bone marrow (AM) internal dosimetry. Up-to-date reference computational phantoms recommended by the ICRP are based on the analysis of CT-images of cadavers. Such phantoms have significant disadvantages. One disadvantage is that the assessment of uncertainty due to the population variability of skeleton dimensions and microstructure results from the limited availability of autopsy material. Another disadvantage is the simplified modelling of cortical layer and bone microarchitecture. A method of stochastic parametric skeletal dosimetry modelling of the bone structures – SPSD modelling – has been developed as an alternative to the ICRP reference phantoms. In the framework of this approach, skeletal phantom parameters are evaluated based on extensively reviewed results of published measurements of real bones. The SPSD approach allows for the assessment of both population-average values and their variability. SPSD-phantoms of the skeleton are modelled in voxel representation. They consist of smaller phantoms of the bone sites – segments – described by simple geometric shapes with uniform microarchitecture parameters. Such segmentation makes it possible to account for non-homogeneous skeletal microarchitecture and to model the bone structure with the required voxel resolution to elaborate suitable skeletal phantoms. The current study presents the parameters of the SPSD skeletal phantoms for the following age-groups: newborn, 1-year-old, 5-year-old, 10-year-old, 15-year-old (male and female), and adult (male and female). This skeletal phantom can be used for dosimetry as an alternative to available reference phantoms for bone-seeking radionuclides. The above-mentioned age- and sex-specific skeletal phantoms are comprised of 289 unique segments. The characteristics of the SPSD phantoms do not contradict published data and are in good agreement with the measurement results of real bones.

Science & Technology - Other Topics↗