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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 199 records · Page 11

Use of Event-Time Embeddings via RNN to Discern Novel Event Sequences in EHRs

In highly configurable health information technology (HIT) systems, such as VistA of the Veterans Health Administration, the variations in how the system is used among different healthcare facilities and how the data are recorded can be significant. Despite the successful standardization of care efforts, some of these variations can be indicative of HIT hazards and demand further investigation. In this work, we implemented a recurrent neural network (RNN) architecture to learn clinical provider order sequences and their temporal dynamics while predicting the orders' terminal state. We demonstrate model performance and provide a use case for the model discerning novel event sequences. This model is proposed to find novel event sequences in an operational environment.

Ozmen, Ozgur↗

Deep Reinforcement Learning-Based Edge Caching in Wireless Networks

With the purpose to offload data traffic in wireless networks, content caching techniques have recently been studied intensively. Using these techniques and caching a portion of the popular files at the local content servers, the users can be served with less delay. Most of the content replacement policies are based on the content popularity, that depends on the users' preferences. In practice, such information varies over time. Therefore, an approach to determine the file popularity patterns must be incorporated into caching policies. In this context, we study content caching at the wireless network edge using a deep reinforcement learning framework with Wolpertinger architecture. In particular, we propose deep actor-critic reinforcement learning based policies for both centralized and decentralized content caching. For centralized edge caching, we aim at maximizing the cache hit rate. In decentralized edge caching, we consider both the cache hit rate and transmission delay as performance metrics. These proposed frameworks are assumed to neither have any prior information on the file popularities nor know the potential variations in such information. Via simulation results, the superiority of the proposed frameworks is verified by comparing them with other policies, including least frequently used (LFU), least recently used (LRU), and first-in-first-out (FIFO) policies.

42 ENGINEERING↗

Cooling and Timing Tests of the ATLAS Fast TracKer VME Boards

The Fast TracKer (FTK) is an ATLAS trigger upgrade built for full-event, low-latency, high-rate tracking. The FTK core, made of 9U VME boards, performs the most demanding computational task. The associative memory board (AMB) serial link processor and the auxiliary card (AUX), plugged on the front and back sides of the same VME slot, constitute the processing unit (PU), which finds tracks using hits from eight layers of the inner detector. The PU works in pipeline with the second stage board (SSB), which finds 12-layer tracks by adding extra hits to the identified tracks. In the designed configuration, 16 PUs and four SSBs are installed in a VME crate. The high power consumption of the AMB, AUX, and SSB (respectively, of about 250, 70, and 160 W per board) required the development of a custom cooling system. Even though the expected power consumption for each VME crate of the FTK system is high compared with a common VME setup, the 8 FTK core crates will use ≈60 kW, which is just a fraction of the power and the space needed for a CPU farm performing the same task. We report on the integration of 32 PUs and eight SSBs inside the FTK system, on the infrastructures needed to run and cool them, and on the tests performed to verify the system processing rate and the temperature stability at a safe value.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus , Pseudomonas aeruginosa , and Francisella tularensis

Abstract Small multidrug resistance transporters efflux toxic compounds from bacteria and are a minimal system to understand multidrug transport. Most previous studies have focused on EmrE, the model SMR from Escherichia coli , finding that EmrE has a broader substrate profile than previously thought and that EmrE may perform multiple types of transport, resulting in substrate‐dependent resistance or susceptibility . Here, we performed a broad screen to identify potential substrates of three other SMRs: PAsmr from Pseudomonas aeruginosa ; FTsmr from Francisella tularensis ; and SAsmr from Staphylococcus aureus . This screen tested metabolic differences in E. coli expressing each transporter versus an inactive mutant, for a clean comparison of sequence and substrate‐specific differences in transporter function, and identified many substrates for each transporter. In general, resistance compounds were charged, and susceptibility substrates were uncharged, but hydrophobicity was not correlated with phenotype. Two resistance hits and two susceptibility hits were validated via growth assays and IC50 calculations. Susceptibility is proposed to occur via substrate‐gated proton leak, and the addition of bicarbonate antagonizes the susceptibility phenotype, consistent with this hypothesis.

Biochemistry & Molecular Biology↗

ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome

Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS.

60 APPLIED LIFE SCIENCES↗

Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2

Targeting the main protease of SARS-CoV-2 Inside host cells, the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is translated into two polyproteins that are cleaved to give the individual viral proteins. The main viral protease, known as Mpro or 3CLpro, plays a key role in these cleavages, making it an important drug target. Drayman et al . identified eight drugs that target 3CLpro from a library of 1900 clinically safe drugs. Because of the challenge of working with SARS-CoV-2, they started by screening for drugs that inhibit the replication of a human coronavirus that causes the common cold. They then evaluated the top hits for inhibiting SARS-CoV-2 replication and for inhibiting 3CLpro. Masitinib, a broad antiviral, inhibited the main proteases of coronaviruses and picornaviruses and was effective in reducing SARS-CoV-2 replication in mice.

Drayman, Nir↗

Sac1 links phosphoinositide turnover to cryptococcal virulence

Cryptococcus neoformans is an environmentally acquired fungal pathogen that causes over 140,000 deaths per year. Cryptococcal infection occurs when infectious particles are deposited into the lung, where they encounter host phagocytic cells. C. neoformans may be engulfed by these phagocytes, an important step of infection that leads to outcomes ranging from termination of infection to cryptococcal dissemination. To study this critical process, we screened approximately 4,700 cryptococcal gene deletion mutants for altered uptake, using primary mouse and human phagocytic cells. Among the hits of these two screens, we identified 93 mutants with perturbed uptake in both systems, as well as others with differences in uptake by only one cell type. We further screened the hits for changes in thickness of the capsule, a protective polysaccharide layer around the cell which is an important cryptococcal virulence factor. The combination of our three screens yielded 45 mutants, including one lacking the phosphatidylinositol-4-phosphate phosphatase Sac1. In this work, we implicate Sac1 in both host cell uptake and capsule production. We found that sac1 mutants exhibit lipid trafficking defects, reductions in secretory system function, and changes in capsule size and composition. Many of these changes occur specifically in tissue culture media, highlighting the role of Sac1 phosphatase activity in responding to the stress of host-like conditions. Overall, these findings show how genome-scale screening can identify cellular factors that contribute to our understanding of cryptococcal biology and demonstrate the role of Sac1 in determining fungal virulence.

59 BASIC BIOLOGICAL SCIENCES↗

Design optimization of MAPS-based detectors using a data-driven fast simulation approach

A parametric simulation tool for pixel sensors is presented. A realistic pixel response is simulated purely based on measurement input, without requiring detailed knowledge of the underlying manufacturing process. As such, it provides an efficient alternative to the use of Technology Computer-Aided Design simulations, which typically depend on proprietary process information. Due to its parametric approach, the package is fast and thus particularly useful for larger detector systems and high hit rate environments. This work presents measurements, simulation and its validation for the MALTA2 sensor. It is a small collection electrode monolithic active pixel sensor produced in the Tower 180 nm complementary metal-oxide-semiconductor imaging process. Modifications to the sensor’s periphery, mainly in the hit merger, are studied in order to optimize the performance for tracking and calorimetry. This optimization is of special interest as part of the MALTA3 sensor redesign in the 65 nm Tower Partners Semiconductor Co. process.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Code Release for “Unlocking Extreme Space Weather through Advanced Modeling of Legacy Vela Spacecraft” ER

The software being developed for this project has two mains aims. First, a Bayesian Model Calibration (BMC) procedure is being developed to calibrate a spallation model that simulates protons hitting a spacecraft orbiting earth to real data. The procedure will be developed for general data (there is no data release requested as part of this code release). Second, an inverse physics modeling task is being undertaken to map the number of resulting neutrons observed from this process to the expected number of protons that hit the model. This second task is of statistical interest; to publish on it, the code will need to be open source.

Murph, Alexander↗

Bigpicc: a graph-based approach to identifying carcinogenic gene combinations from mutation data

Abstract Genome data from cancer patients represents relationships between the presence of a gene mutation and cancer occurrence in a patient. Different types of cancer in human are thought to be caused by combinations of two to nine gene mutations. Identifying these combinations through traditional exhaustive search requires the amount of computation that scales exponentially with the combination size and in most cases is intractable even for cutting-edge supercomputers. We propose a parameter-free heuristic approach that leverages the intrinsic topology of gene-patient mutations to identify carcinogenic combinations. The biological relevance of the identified combinations is measured by using them to predict the presence of tumor in previously unseen samples. The resulting classifiers for 16 cancer types perform on par with exhaustive search results, and score the average of 80.1% sensitivity and 91.6% specificity for the best choice of hit range per cancer type. Our approach is able to find higher-hit carcinogenic combinations targeting which would take years of computations using exhaustive search.

Biochemistry & Molecular Biology↗

Draft genome of multiple resistance donor plant Sinapis alba: An insight into SSRs, annotations and phylogenetics

Sinapis alba is a wild member of the Brassicaceae family reported to possess genetic resistance against major biotic and abiotic stresses of oilseed brassicas. However, the resistance nature of S. alba was not exploited generously due to the unavailability of usable genome sequences in public databases. Therefore, the present study was conducted to assemble the first draft genome from raw whole genome shotgun sequences with annotation and develop simple sequence repeat markers for molecular genetics and marker-assisted breeding. Results The raw genome sequences had 96x coverage on the Illumina platform with 170 Gbp data. The developed assembly by SOAPdenovo2 has ~459 Mbp genome size covered in 403,423 contigs with an average size of 1138.04 bp. The assembly was BLASTX with Arabidopsis thaliana which showed 32.9% positive hits between both plants. The top hit species distribution analysis showed the highest similarity with A. thaliana. A total of 809,597 GO level annotations were recorded after BLASTX results, and 34,012 sequences were annotated with different enzyme codes grouped under seven classes. The gene prediction tool AUGUSTUS identified 113,107 probable genes with an average size of 684 bp. The biochemical pathway annotation assigned 16,119 potential genes to 152 KEGG maps and 1751 enzyme codes. The development of potential SSRs from the de-novo assembly yielded 70731 unique primer pairs. Out of 159 randomly selected SSR markers for validation, 149 successfully amplified in S. alba. However, 10 SSR markers did not amplify during the validation experiment. Conclusion The annotated genome assembly with a large number of SSRs was developed in the present study. To the best of our knowledge, this is the first report of S. alba genome assembly development, annotation, and SSRs mining to date. The data presented here will be a very important resource for future crop improvement programs, especially for resistant breeding.

59 BASIC BIOLOGICAL SCIENCES↗

High-throughput screening of the ReFRAME, Pandemic Box, and COVID Box drug repurposing libraries against SARS-CoV-2 nsp15 endoribonuclease to identify small-molecule inhibitors of viral activity

SARS-CoV-2 has caused a global pandemic, and has taken over 1.7 million lives as of mid-December, 2020. Although great progress has been made in the development of effective countermeasures, with several pharmaceutical companies approved or poised to deliver vaccines to market, there is still an unmet need of essential antiviral drugs with therapeutic impact for the treatment of moderate-to-severe COVID-19. Towards this goal, a high-throughput assay was used to screen SARS-CoV-2 nsp15 uracil-dependent endonuclease (endoU) function against 13 thousand compounds from drug and lead repurposing compound libraries. While over 80% of initial hit compounds were pan-assay inhibitory compounds, three hits were confirmed as nsp15 endoU inhibitors in the 1–20 μM range in vitro. Furthermore, Exebryl-1, a ß-amyloid anti-aggregation molecule for Alzheimer’s therapy, was shown to have antiviral activity between 10 to 66 μM, in Vero 76, Caco-2, and Calu-3 cells. Although the inhibitory concentrations determined for Exebryl-1 exceed those recommended for therapeutic intervention, our findings show great promise for further optimization of Exebryl-1 as an nsp15 endoU inhibitor and as a SARS-CoV-2 antiviral.

60 APPLIED LIFE SCIENCES↗

Development of a pattern recognition algorithm for reconstructing multi-particle events in the Mu2e detector

Mu2e is an upcoming experiment at Fermilab and its main goal is to search for the Charged Lepton Flavor Violation (CLFV) in the coherent transition of a muon into an electron on an Al target. In Mu2e, multi-particle events can occur simultaneously within the same time region and it is crucial to accurately identify each particle track, including signals, to improve the robustness of track finding methods and enhance reconstruction efficiency. ¯p annihilation is one of the background events and produces multiple particles that can mimic signal events. Additionally, photons from radiative pion captures can produce a γ → $e+e−$ pair, which can be used to calibrate the Mu2e momentum scale and the resolution. The Mu2e track reconstruction sequence begins by grouping hits produced in the tracker based on time and z coordinate information, called TimeCluster, and selected hits are processed to reconstruct helices and determine their momentum. The current pattern recognition algorithms identify a single helix per TimeCluster for single track events. A new pattern recognition algorithm is being developed to reconstruct multi-particle events and its features for finding multiple tracks and the current evaluation results are reported.

Kitagawa, H. [Pisa U.]↗

6D Simulations of PIP-II Booster Injection

The PIP-II superconducting linac will deliver 2 mA average H⁻ beam current at 800 MeV to the existing Booster synchrotron over a period of 0.55 ms (285 turns). As a result, the injected beam power will quadruple to 17 kW. Safe operation at the increased beam power implies careful attention to the origin, magnitude, and distribution of both controlled and uncontrolled losses. Uncontrolled losses are due to neutral ions in excited states stripped in downstream magnets and large angle scattered protons from parasitic foil hits. The relative magnitudes of these loss mechanisms is used to determine the optimal foil thickness. A transverse painting scheme involving closed orbit motion will be used to mitigate space charge effects and minimize parasitic foil hits. Using a detailed full 6D simulation of the injection process, we compute large angle scattering losses and compare results to back of the envelope estimates. We investigate possible impact of space charge on the emittance and beam distribution both during and at the conclusion of the injection period.

43 PARTICLE ACCELERATORS↗

Challenges and Optimization of Mu2e Proton Target Design with Radiative Cooling

Mu2e, the Muon-to-Electron Conversion Experiment, aims to identify physics beyond the Standard Model, namely, the conversion of muons to electrons without the emission of neutrinos. The muons are produced from pions generated in a production target when it is hit by an 8 GeV proton beam from the Fermilab Booster/Main Injector. The proton target design space is strongly constrained by a one-year operating lifetime and the need for radiative cooling in a vacuum environment. Uncertainties in the lifetime of the existing baseline design – a monolithic, segmented tungsten target – are large, particularly due to unknown impacts of radiation damage at the very high proton fluences expected in the experiment. We have begun evaluation of a new design utilizing Inconel 718 over the WL10 used in the existing target design. As a result, the structural design of the target has evolved significantly. This evolution focuses on lowering the target temperature, minimizing obstruction to muons, increasing structural stability, maximizing fatigue lifetime, simplifying the fabrication process, and more. The thermal management, structural stability and fatigue lifetime are emphasized here. These optimizations have led to a promising new target design for the Mu2e experiment.

Liu, Z. [Fermilab]↗

Ultra High Performance Liquid Chromatography with Quadrupole Time-of-Flight Mass Spectrometry and Fisher Ratio Analysis for Discovery-Based Analysis

The ability to discover minute differences between samples or sample classes for ultrahigh performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) can be a challenging endeavor especially when these differences are not known a priori. Indeed a typical UHPLC-QTOF analysis time of ~15 minutes can generate over 4 gigabytes of information for a single sample. Implementation of chemometrics such as Fisher ratio (F-ratio) analysis will allow the analyst to quickly and precise probe the chemical differences between different samples or sample classes. F-ratio analysis can be used to find sample or sample class distinguishing compounds reducing the 5 gigabytes of information into a simple, yet informative hit list. Moreover through combinatorial rearrangement, it is possible to determine a F-ratio threshold to separate the real and non-real hits. The F-ratio software presented herein is a semi-automated algorithm that processes the raw, exported .csv files from the SCIEX 500R QTOF in as little as 30 seconds. While further research is needed to modify and perfect the software to deal with high resolution mass spectra precise to 0.0001 Daltons, the current software, precise to 0.1 Da, is able to find significant chemical differences despite some of them being at extremely low concentrations nearing the limit of detection.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

3D-Reconstruction of Tau Neutrinos in LArTPC Detectors

The Deep Underground Neutrino Experiment (DUNE) is a next-generation neutrino experiment currently under construction. DUNE will consist of two high-resolution neutrino interaction imaging detectors exposed to the world’s most intense neutrino beam, with the Near Detector at Fermilab and the Far Detector 1,300 km away in the Sanford Underground Research Facility in South Dakota, US. The high statistics and excellent resolution capabilities of DUNE's $^{40}$Ar detector will allow us to make precision studies of oscillation parameters capable of searching for CP violation in the lepton sector, testing interaction models, and studying phenomena that have until now, seemed too complex to measure, like $\nu_\tau$ detection and therefore, providing the completion of the 3-flavor neutrino paradigm. Knowledge of the $\nu_\tau$ detection can impact a broad spectrum of open questions. These include searching for non-standard neutrino interactions, constraining the unitarity of the PMNS matrix, searching for sterile neutrinos, and studying neutrino interactions. In the case of LArTPC data, the detector hits can be considered nodes in a graph, and the edges represent the spatial and temporal relationships between them. By using graph neural networks, it is possible to exploit these relationships and improve the accuracy of particle identification and reconstruction. During my presentation and specifically for tau neutrino reconstruction, I will show the effectiveness and reliability of our in-house developed graph neural network (GNN), NuGraph. This GNN classifies detector hits based on the particle type responsible for their production, assuring that the system accurately identifies and categorizes information based on its unique characteristics.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Neutron Identification Capabilities in MicroBooNE Through the Application of Machine Learning with Blips

Neutrinos (ν) are subatomic particles first observed in 1956 by LANL physicists Clyde Cowan and Frederick Reines but first theorized by Wolfgang Pauli in 1930. Neutrinos are the least massive known particle and are classified as leptons with 3 flavors corresponding to their leptonic counterparts (electron, muon, and tau). We know that they are abundant, 65 billion neutrinos travel through your fingertip every second, and elusive, a single neutrino could fly through a lightyear of lead without interacting at all. Though, there is much still unknown and a better characterization of these “ghostly” particles can give us clues as to the matter/anti-matter asymmetry in the early universe and possible glimpses into new physics. To measure a particle that is extremely light and rarely interacting, physicists have developed an extremely sensitive detector known as a Liquid Argon Time Projection Chamber (LArTPC). The fiducial volume (or TPC) is bombarded with neutrinos, some of which interact with argon (Ar) atoms to produce particles that in turn excite and ionize the Ar. The products of these are free electrons which then drift through the TPC’s applied magnetic field towards a multi-plane wire readout system. The electrons’ charge is collected at this anode and the light from the initial interactions is collected by photomultiplier tubes (PMTs). In conjunction, these mechanisms allow LArTPCs to achieve millimeter spatial resolution and sub-MeV energy thresholds. The detector of interest in this study is the MicroBooNE Experiment at Fermilab. MicroBooNE is an above ground LArTPC with dimensions of approximately 10m × 2.5m × 2.3m, about the size of a school bus. Its purpose is to study neutrinos, so to improve rates of measured ν interactions, the detector is squarely in the path of the Booster Neutrino Beam (BNB) at Fermilab. A major challenge in neutrino studies is energy reconstruction, much of the neutrino’s original energy is lost in interactions that the detector is not sensitive to, often due to low-energy products. The initial goal of this analysis was to better identify neutrons, the main source of poor energy reconstruction in neutrino events. Because neutrons are neutral particles, like neutrinos, we can only directly measure the products of their interactions in LArTPCs. Most of these products are low-energy signals and while each one contributes a negligible amount of energy, collectively these signals make up most of the lost energy in each neutrino event. We define these signals as blips; point-like, isolated depositions of charge in the detector. Blips have MeV-scale energies and are the size of a single hit (charge deposition) or a cluster of a few hits on at least two wire planes. Blips are the principal detector features used to study low-energy physics; thus, they are the key to unlocking information not only about neutrons but gamma photons, supernova and solar neutrinos as well as helping us better identify certain particles. Therefore, this analysis strives to use blips for improved neutron identification (ID) and characterization.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗