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All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

A variational method for the sheath potential of hypersonic leading edges with space-charge limitations

Electron transpiration cooling for the leading edges (LE) of hypersonic aircraft utilizes thermionic emission; however, space-charge effects limit the electron emission rate, potentially diminishing the efficiency of this cooling mechanism. We develop a variational weak form of the Poisson equation that describes the sheath potential and then numerically solve it using the finite element method. This formulation has two main benefits: (1) the space-charge limit condition can be incorporated as a constraint and (2) it allows for the analysis of three-dimensional geometries with complex boundary conditions. We demonstrate that the current emitted from the surface of an LE is generally a small fraction of the Child–Langmuir limit due to space charge. We then propose several methods to enhance the emitted current from the surface and to boost the cooling effect of thermionic emission. These include increasing the plasma density, applying a negative surface potential, and using fringe fields under suitable geometric conditions. For a LaB6 emitting LE, the total emitted current is shown to be minimal and independent of the temperature of a surface with floating potential. However, when a negative potential is applied and the surface is heated, the emitted current follows the Richardson–Dushman relationship up to a critical temperature, beyond which it remains constant. At an applied surface potential of −5 V, the critical temperature is around 1700 K.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2025

Nonlocal, diamagnetic electromagnetic effects in magnetically insulated transmission lines

We identify the time-dependent physics responsible for the critical reduction of current losses in magnetically insulated transmission lines (MITLs) due to uninsulated space charge-limited currents of electrons emitted by field stress. A drive current of sufficiently short pulse length introduces a strong enough time dependence that steady-state results alone become inadequate for the complete understanding of current losses. The time-dependent physics can be described as a nonlocal, diamagnetic electromagnetic response of space charge limited currents. As the pulse length is increased or equivalently, the MITL length reduced, these time-dependent effects diminish and current losses converge to those predicted by the well-known Child–Langmuir law in the external (vacuum) fields. We present a simple one-dimensional (1D) model that encapsulates the essence of this physics. We find excellent agreement with 2D particle-in-cell simulations for two MITL geometries, Cartesian parallel plate and azimuthally symmetric straight coaxial. Based on the 1D model, we explore various scaling dependencies of MITL losses with relevant parameters, e.g., peak current, pulse length, geometrical dimensions, etc. We propose an improved physics model of magnetic insulation in the form of a Hull curve, which could also help improve predictions of current losses by common circuit element codes, such as BERTHA. Finally, we describe how to calculate the temperature rise due to electron impact within the 1D model.

Computer simulation↗
DOE OSTI2025

Extending the Mott–Gurney law to one-dimensional nonplanar diodes using point transformations

Recent studies have applied variational calculus, conformal mapping, and point transformations to generalize the one-dimensional (1D) space-charge limited current density (SCLCD) and electron emission mechanisms to nonplanar geometries; however, these assessments have focused on extending the Child–Langmuir law (CLL) for SCLCD in vacuum. Since the charge in the diode is independent of the coordinate system (i.e., covariant), we apply bijective point transformations to extend the Mott–Gurney law (MGL) for the SCLCD in a collisional or semiconductor gap to nonplanar 1D geometries. This yields a modified MGL that replaces the Cartesian gap distance with a canonical gap distance that may be written generally in terms of geometric scale factors that are known for multiple geometries. We tabulate results for common geometries. Such an approach may be applied to any current density, including non-space-charge limited gaps and SCLCD that may fall between the CLL and MGL.

Garner, Allen L. [Purdue Univ., West Lafayette, IN↗
DOE OSTI2021

Cardinal: A Lower-Length-Scale Multiphysics Simulator for Pebble-Bed Reactors

This paper demonstrates a multiphysics solver for pebble-bed reactors, in particular, for Berkeley’s pebble-bed -fluoride-salt-cooled high-temperature reactor (PB-FHR) (Mark I design). The FHR is a class of advanced nuclear reactors that combines the robust coated particle fuel form from high-temperature gas-cooled reactors, the direct reactor auxiliary cooling system passive decay removal of liquid-metal fast reactors, and the transparent, high-volumetric heat capacitance liquid-fluoride salt working fluids (e.g., FLiBe) from molten salt reactors. This fuel and coolant combination enables FHRs to operate in a high-temperature, low-pressure design space that has beneficial safety and economic implications. The PB-FHR relies on a pebble-bed approach, and pebble-bed reactors are, in a sense, the poster child for multiscale analysis. Relying heavily on the MultiApp capability of the Multiphysics Object-Oriented Simulation Environment (MOOSE), we have developed Cardinal, a new platform for lower-length-scale simulation of pebble-bed cores. The lower-length-scale simulator comprises three physics: neutronics (OpenMC), thermal fluids (Nek5000/NekRS), and fuel performance (BISON). Cardinal tightly couples all three physics and leverages advances in MOOSE, such as the MultiApp system and the concept of MOOSE-wrapped applications. Moreover, Cardinal can utilize graphics processing units for accelerating solutions. In this paper, we discuss the development of Cardinal and the verification and validation and demonstration simulations.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2024

Describing patterns of familial cancer risk in subfertile men using population pedigree data

STUDY QUESTION Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER Here, distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966–2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS Azoospermic (0 × 10 6 /mL) and severely oligozoospermic (<1.5 × 10 6 /mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966–2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48–4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01–2.39), uterine cancers HR = 1.27 (95% CI = 1.03–1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07–2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21–1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01–1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30–4.54), and testis cancer HR = 2.34 (95% CI = 1.60–3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16–0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96–2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64–12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1–3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19–2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84–9.32). LIMITATIONS, REASONS FOR CAUTION Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Realistic galaxy image simulation via score-based generative models

ABSTRACT We show that a denoising diffusion probabilistic model (DDPM), a class of score-based generative model, can be used to produce realistic mock images that mimic observations of galaxies. Our method is tested with Dark Energy Spectroscopic Instrument (DESI) grz imaging of galaxies from the Photometry and Rotation curve OBservations from Extragalactic Surveys (PROBES) sample and galaxies selected from the Sloan Digital Sky Survey. Subjectively, the generated galaxies are highly realistic when compared with samples from the real data set. We quantify the similarity by borrowing from the deep generative learning literature, using the ‘Fréchet inception distance’ to test for subjective and morphological similarity. We also introduce the ‘synthetic galaxy distance’ metric to compare the emergent physical properties (such as total magnitude, colour, and half-light radius) of a ground truth parent and synthesized child data set. We argue that the DDPM approach produces sharper and more realistic images than other generative methods such as adversarial networks (with the downside of more costly inference), and could be used to produce large samples of synthetic observations tailored to a specific imaging survey. We demonstrate two potential uses of the DDPM: (1) accurate inpainting of occluded data, such as satellite trails, and (2) domain transfer, where new input images can be processed to mimic the properties of the DDPM training set. Here we ‘DESI-fy’ cartoon images as a proof of concept for domain transfer. Finally, we suggest potential applications for score-based approaches that could motivate further research on this topic within the astronomical community.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2022

Symptomatic Plasmodium vivax Infection in Rwanda

Here, we report a Plasmodium vivax infection in a Rwandan child misdiagnosed with Plasmodium falciparum and administered artemether-lumefantrine. Antigen detection revealed an absence of P falciparum histidine-rich protein 2 (HRP2) and presence of Plasmodium vivax lactate dehydrogenase. Nested and real-time polymerase chain reactions verified that the sample only contained P vivax deoxyribonucleic acid.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Combined computed tomography and position-resolved X-ray diffraction of an intact Roman-era Egyptian portrait mummy

Hawara Portrait Mummy 4, a Roman-era Egyptian portrait mummy, was studied with computed tomography (CT) and with CT-guided synchrotron X-ray diffraction mapping. These are the first X-ray diffraction results obtained non-invasively from objects within a mummy. The CT data showed human remains of a 5-year-old child, consistent with the female (but not the age) depicted on the portrait. Physical trauma was not evident in the skeleton. Diffraction at two different mummy-to-detector separations allowed volumetric mapping of features including wires and inclusions within the wrappings and the skull and femora. Additionally, the largest uncertainty in origin determination was approximately 1.5 mm along the X-ray beam direction, and diffraction- and CT-determined positions matched. Diffraction showed that the wires were a modern dual-phase steel and showed that the 7 × 5 × 3 mm inclusion ventral of the abdomen was calcite. Tracing the 00.2 and 00.4 carbonated apatite (bone's crystalline phase) reflections back to their origins produced cross-sectional maps of the skull and of femora; these maps agreed with transverse CT slices within approximately 1 mm. Coupling CT and position-resolved X-ray diffraction, therefore, offers considerable promise for non-invasive studies of mummies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Measuring the growth of Alfvén wave parametric decay instability using counter-propagating waves: Theory and simulations

The parametric decay instability (PDI) of Alfvén waves—where a pump Alfvén wave decays into a backward-propagating child Alfvén wave and a forward ion acoustic wave—is a fundamental nonlinear wave-wave interaction and holds significant implications for space and laboratory plasmas. However, to date there has been no direct experimental measurement of PDI. Here, we propose a novel and experimentally viable scheme to quantify the growth of Alfvén wave PDI on a linear device using a large pump Alfvén wave and a small counter-propagating seed Alfvén wave, with the seed-wave frequency tuned to match the backward Alfvén wave generated by standard PDI. Using hybrid simulations, we show that energy transfer from the pump to the seed reduces the latter's spatial damping. By comparing seed-wave amplitudes with and without the pump wave, this damping reduction can be used as a direct and reliable proxy for PDI growth. The method is validated in our simulations across a range of plasma and wave parameters and agrees well with theoretical predictions. Notably, the scheme exhibits no threshold for PDI excitation and is, in principle, readily implementable under current laboratory conditions. Finally, this scheme is a critical step toward solving the challenge of experimentally accessing Alfvén wave PDI and provides an elegant method that may be used to validate fundamental theories of parametric instabilities in controlled laboratory settings.

heliosphere↗
DOE OSTI2024

First measurement of the yield of 8 He isotopes produced in liquid scintillator by cosmic-ray muons at Daya Bay

Here, Daya Bay presents the first measurement of cosmogenic 8 He isotope production in liquid scintillator, using an innovative method for identifying cascade decays of 8 He and its child isotope, 8 Li. We also measure the production yield of 9 Li isotopes using well-established methodology. The results, in units of 10 –8 μ –1 ⁢g –1 cm 2 , are 0.307 ± 0.042, 0.341 ± 0.040, and 0.546 ± 0.076 for 8 He, and 6.73 ± 0.73, 6.75 ± 0.70, and 13.74 ± 0.82 for 9 Li at average muon energies of 63.9 GeV, 64.7 GeV, and 143.0 GeV, respectively. The measured production rate of 8 He isotopes is more than an order of magnitude lower than any other measurement of cosmogenic isotope production. It replaces the results of previous attempts to determine the ratio of 8 He to 9 Li production that yielded a wide range of limits from 0% to 30%. The results provide future liquid-scintillator-based experiments with improved ability to predict cosmogenic backgrounds.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2025

The Implications of Collisions on the Spatial Profile of Electric Potential and the Space-Charge-Limited Current

The space-charge-limited current (SCLC) in a vacuum diode is given by the Child-Langmuir law (CLL), whose electric potential ϕ(x) ∝ (x/D) 4/3 , where x is the spatial coordinate across the gap and D is the gap separation distance. For a collisional diode, SCLC is given by the Mott-Gurney law (MGL) and ϕ(x) ∝ (x/D) 3/2 . Here, we apply a capacitance argument for SCLC and use the transit time from a recent exact solution for collisional SCLC to show that ϕ(x) ∝ (x/D)ξ for a general collisional gap, where 4/3 ≤ ξ ≤ 3/2 . Furthermore, ξ is strictly a function of νT, where ν is the collision frequency and T is the electron transit time. Using this definition of ξ, we estimate the spatial dependence of the electron velocity and use the gap capacitance to derive an analytic equation for collisional SCLC that agrees within ~4.5% of the exact solution that requires solving parametrically through T. This analytic equation for general ξ asymptotically recovers the CLL as ν → 0 and the MGL as ν → ∞. As a result, matching these limits shows that ξ ≈ 1.40 and V ∝ D 2 ν 2 at the transition from a vacuum to a collisional diode for any device condition.

Anodes↗
DOE OSTI2020

Analyzing the Performance Trade-Off in Implementing User-Level Threads

User-level threads have been widely adopted as a means of achieving lightweight concurrent execution without the costs of OS-level threads. Nevertheless, the costs of managing user-level threads represent a performance barrier that dictates how fine grained the concurrency exposed by an application can be without incurring significant overheads; this in turn may translate into insufficient parallelism to exploit highly parallel systems. This article is a deep dive into the fundamental costs in implementing user-level threads. We first identify that one of the highest sources of fork-join overheads stems from deviations, events that incur context switching during the execution of a thread and disrupt a run-to-completion execution. We then conduct an in-depth investigation of a wide spectrum of methods with respect to how they handle deviations while covering both parent- and child-first scheduling policies. Our methodology involves a comprehensive instruction- and cache-level analysis of all methods on several modern CPU architectures. Finally, the primary finding of our evaluation is that dynamic promotion methods that assume the absence of deviation and dynamically provide context-switching support offer the best trade-off between performance and capability when the likelihood of deviation is low.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

A Review of Doses for Dental Imaging in 2010–2020 and Development of a Web Dose Calculator

Dental imaging is one of the most common types of diagnostic radiological procedures in modern medicine. We introduce a comprehensive table of organ doses received by patients in dental imaging procedures extracted from literature and a new web application to visualize the summarized dose information. We analyzed articles, published after 2010, from PubMed on organ and effective doses delivered by dental imaging procedures, including intraoral radiography, panoramic radiography, and cone-beam computed tomography (CBCT), and summarized doses by dosimetry method, machine model, patient age, and technical parameters. Mean effective doses delivered by intraoral, 1.32 (0.60–2.56) μSv, and panoramic, 17.93 (3.47–75.00) μSv, procedures were found to be about1% and 15% of that delivered by CBCT, 121.09 (17.10–392.20) μSv, respectively. In CBCT imaging, child phantoms received about 29% more effective dose than the adult phantoms received. The effective dose of a large field of view (FOV) (>150 cm2) was about 1.6 times greater than that of a small FOV (<50 cm2). The maximum CBCT effective dose with a large FOV for children, 392.2 μSv, was about 13% of theeffective dose that a person receives on average every year from natural radiation, 3110 μSv. Monte Carlo simulations of representative cases of the three dental imaging procedures were then conducted to estimate and visualize the dose distribution within the head. The user-friendly interactive web application (available at http://dentaldose.org) receives user input, such as the number of intraoral radiographs taken, and displays total organ and effective doses, dose distribution maps, and a comparison with other medical and natural sources of radiation. The web dose calculator provides a practical resource for patients interested in understanding the radiation doses delivered by dental imaging procedures.

Lee, Hawon↗
DOE OSTI2025

DEMographic MicrOSimulation (DEMOS) v2.0

DEMOS is an agent-based simulation framework used to evolve population demographic characteristics or lifecycle events such as education, marital status etc. DEMOS modules are designed to capture the interdependencies of short-term and long-term lifecycle events often influential in downstream transportation and land use modeling. An important facet of DEMOS is that it is dynamic, meaning it captures the impact of an agent's demographic characteristics in year 't' on their demographic status in year 't+1'. This has important consequences on medium- and long-term downstream modeling in different domains, such as transportation where decisions such as household vehicle transactions (i.e., buying, selling, or replacing a vehicle) depend current or past household vehicle holdings as well as household transitions. Other downstream modeling that can be enabled by DEMOS include building technology adoption or retrofit decisions, and more. DEMOS modules include: individual age progression year by year, individual mortality events, household restructuring events including marriage match-making; household birth events; individual education participation; individual labor force participation; child leaving household; household in-migration and out-migration for the region; household residence location choice and household mandatory destination choice (work and school). This version of DEMOS is tailored to be integrated with the land use simulation software UrbanSim.

Caicedo, Juan [UrbanSim, Inc.]↗
DOE OSTI2025

An Open-source Llm Enhanced-tool Specialized In Helping Moose Related Problems And Tasks

MOOSEenger is an open-source, terminal-first chat application for the MOOSE ecosystem that couples specialized parsing of MOOSE documentation and “.i” input files with retrieval-augmented generation to deliver grounded answers about multiphysics modeling and workflows. It includes dedicated readers for MOOSE-style HTML and a pyhit-based parser that uses the MOOSE syntax tree to preserve block structure and attach retrieval metadata. A data-ingestion pipeline performs semantic chunking into atomic facts and stores them hierarchically in a local Chroma vector database that maintains parent–child relationships across documents; the system can ingest directories, individual files, and single-page web content, and it provides CRUD operations (insert, update, delete) to manage the corpus. At query time, relevant chunks are embedded, retrieved, and fused into the model context, with interactive features such as token streaming, persistent chat history, and dynamic RAG (retrieval triggered by user input or intermediate model output). Deployment is flexible: MOOSEenger runs with local Ollama models or remote Hugging Face/OpenAI backends—typically coordinating generation, lightweight tagging/summarization, and embeddings across three models—and it also supports a server mode and integration with the VS Code Continue interface.

Li, Mengnan [Idaho National Laboratory (INL), Idah↗
DOE OSTI2020

Children, Income, and the Impact of Home Delivery on Household Shopping Trips

Expanding e-commerce and delivery benefit consumers through increased flexibility and convenience. However, there is a potential impact on vehicle miles traveled (VMT) by delivery and personal vehicles, and the resulting energy consumption, air quality, and congestion. Delivery trips could replace personal vehicle trips, but, if not a replacement, could add to (or supplement) shopping-related VMT for a given household. Here, we examined the benefits of e-commerce to consumers and the impact on personal shopping trips, and how these differed across item types, household child status, and income. We found that high-income households and households with children cared relatively more about time saving from deliveries. We found that, on average, deliveries substituted for 12% of vehicle shopping trips, but supplemented personal shopping trips for 9% of purchase deliveries. Underlying these averages were two main types of households: those for whom all deliveries substitute for trips (between 55% and 70% of households) and those for whom all deliveries supplement trips (between 20% and 35% of households). There was significant heterogeneity across households with and without children and with high or low incomes with respect to the use of delivery. Although time savings were more likely to motivate higher-income households and households with children to use delivery, this did not translate through to these households substituting for more of their trips; deliveries of prepared meals for both these categories of household were relatively more likely (15% for households with children, and 12% for higher-income households) to supplement, and not substitute for, personal trips.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2022

Profiling the BLAST bioinformatics application for load balancing on high-performance computing clusters

Abstract Background The Basic Local Alignment Search Tool (BLAST) is a suite of commonly used algorithms for identifying matches between biological sequences. The user supplies a database file and query file of sequences for BLAST to find identical sequences between the two. The typical millions of database and query sequences make BLAST computationally challenging but also well suited for parallelization on high-performance computing clusters. The efficacy of parallelization depends on the data partitioning, where the optimal data partitioning relies on an accurate performance model. In previous studies, a BLAST job was sped up by 27 times by partitioning the database and query among thousands of processor nodes. However, the optimality of the partitioning method was not studied. Unlike BLAST performance models proposed in the literature that usually have problem size and hardware configuration as the only variables, the execution time of a BLAST job is a function of database size, query size, and hardware capability. In this work, the nucleotide BLAST application BLASTN was profiled using three methods: shell-level profiling with the Unix “time” command, code-level profiling with the built-in “profiler” module, and system-level profiling with the Unix “gprof” program. The runtimes were measured for six node types, using six different database files and 15 query files, on a heterogeneous HPC cluster with 500+ nodes. The empirical measurement data were fitted with quadratic functions to develop performance models that were used to guide the data parallelization for BLASTN jobs. Results Profiling results showed that BLASTN contains more than 34,500 different functions, but a single function, RunMTBySplitDB, takes 99.12% of the total runtime. Among its 53 child functions, five core functions were identified to make up 92.12% of the overall BLASTN runtime. Based on the performance models, static load balancing algorithms can be applied to the BLASTN input data to minimize the runtime of the longest job on an HPC cluster. Four test cases being run on homogeneous and heterogeneous clusters were tested. Experiment results showed that the runtime can be reduced by 81% on a homogeneous cluster and by 20% on a heterogeneous cluster by re-distributing the workload. Discussion Optimal data partitioning can improve BLASTN’s overall runtime 5.4-fold in comparison with dividing the database and query into the same number of fragments. The proposed methodology can be used in the other applications in the BLAST+ suite or any other application as long as source code is available.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development

Hypomyelination, a neurological disorder characterized by a decrease in the production of myelin sheets by glial cells, often has no known etiology. Elucidating the genetic causes of hypomyelination provides a better understanding of myelination, as well as means to diagnose, council, and treat patients. Here, we present evidence that YIPPEE LIKE 3 (YPEL3), a gene whose developmental role was previously unknown, is required for central and peripheral glial cell development. We identified a child with a constellation of clinical features including cerebral hypomyelination, abnormal peripheral nerve conduction, hypotonia, areflexia, and hypertrophic peripheral nerves. Exome and genome sequencing revealed a de novo mutation that creates a frameshift in the open reading frame of YPEL3 , leading to an early stop codon. We used zebrafish as a model system to validate that YPEL3 mutations are causative of neuropathy. We found that ypel3 isexpressed in the zebrafish central and peripheral nervous system. Using CRISPR/Cas9 technology, we created zebrafish mutants carrying a genomic lesion similar to that of the patient. Our analysis revealed that Ypel3 is required for specification and migration of myelinating oligodendrocytes, timely exit of the perineurial glial precursors from the central nervous system (CNS), formation of the perineurium, and Schwann cell maturation. Consistent with these observations, zebrafish ypel3 mutants have metabolomic signatures characteristic of oligodendrocyte and Schwann cell differentiation defects, show decreased levels of Myelin basic protein in the central and peripheral nervous system, and develop defasciculated peripheral nerves. Locomotion defects were observed in adult zebrafish ypel3 mutants. These studies demonstrate that Ypel3 is a novel gene required for perineurial cell differentiation and glial myelination.

59 BASIC BIOLOGICAL SCIENCES↗