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At least 163 records · Page 9

Failure investigation and mitigation after experimental research reactor fuel plate deformation in an irradiation device

Experimental research reactor fuel testing is conducted in the Belgian Reactor 2 (BR2) of the Belgian Nuclear Research Centre (SCK CEN) in dedicated irradiation vehicles or rigs. One such vehicle allows flat full-size fuel plates to be irradiated by inserting them into slotted baskets that captures a narrow portion of the longitudinal edges of the plates. The motion of the fuel plates within the baskets is possible within the narrow slots and thus, the plate is considered to be unattached. The design intentionally omits fixing mechanisms of the fuel plates to the baskets to facilitate the inspection and repositioning of the plates between the irradiation cycles and the accommodation of thermal expansion of the plates in the lateral direction. However, loosely inserted fuel plates have weak structural boundary conditions allowing for larger out-of-plane deflections caused by hydrodynamic loads exerted by the flowing coolant, as compared to those of fixed plates. Unexpected large deformations of plates occurred in several irradiation cycles that further resulted in a loss of cladding integrity. These deformations could not be attributed to a single source. This triggered a series of thermal hydraulic, structural, and fluid-structure interaction analyses aiming at understanding the observed phenomenon. The analyses revealed that, for a certain combination of unfavorable manufacturing and assembly tolerances, fuel plate edges could escape out of the slots in the irradiation basket due to the hydrodynamic load. Subsequently, the plate could become wedged inside the basket coolant channel opening. This resulted in reduced coolant flow and accelerated temperature increase and thermal expansion of the plate while under irradiation. This unfavorable feedback loop could then lead to excessive plate surface temperatures, deformed plates and cladding failure, as was observed in the experiments. These analyses not only provided a probable cause of the fuel plate failures, but also resulted in a new and improved design of the irradiation basket to avoid these issues in the future. In conclusion, a series of recent successful irradiations confirm that the sources of failures were identified correctly, and the implemented mitigations were adequate.

BR2↗

VHH antibody loop guides design of a synthetic macrocyclic peptide that potently blocks influenza virus membrane fusion

Abstract Miniaturizing biologically complex structural motifs to produce synthetic functional mimetics holds significant promise for development of new therapeutic modalities. Here, we demonstrate a unique approach using the key binding loop of the single variable domain of a heavy chain (V H H) llama antibody as a starting point for peptide design. V H H antibodies of camelids and sharks generally have longer, but more ligand-efficient complementarity determining region 3 (CDR3) loops and are relatively stable structures. We harnessed these attributes as templates for design of a series of synthetic macrocyclic peptides. The designed peptides exhibit nanomolar binding to influenza hemagglutinin (HA) and heterosubtypic in vitro neutralization breadth against influenza A viruses by inhibiting the low pH mediated HA conformational changes that lead to membrane fusion. X-ray structures of peptide-HA complexes reveal high structural mimicry with the parent V H H antibody. One such macrocycle peptide candidate is promising for further development of broad protection against influenza A group 1 viruses.

Kadam, Rameshwar U.↗

Analysis and modeling of a family of two-transistor parallel inverters

A family of five static dc-to-square-wave inverters, each employing a square-loop magnetic core in conjunction with two switching transistors, is analyzed using piecewise-linear models for the nonlinear characteristics of the transistors, diodes, and saturable-core devices. Four of the inverters are analyzed in detail for the first time. These analyses show that, by proper choice of a frame of reference, each of the five quite differently appearing inverter circuits can be described by a common equivalent circuit. This equivalent circuit consists of a five-segment nonlinear resistor, a nonlinear saturable reactor, and a linear capacitor. Thus, by proper interpretation and identification of the parameters in the different circuits, the results of a detailed solution for one of the inverter circuits provide similar information and insight into the local and global behavior of each inverter in the family.

Lee, F. C. Y.↗

Human-in-the-Loop Assessment of Alternative Clearances in Interval Management Arrival Operations

Interval Management Alternative Clearances (IMAC) was a human-in-the-loop simulation experiment conducted to explore the Air Traffic Management (ATM) Technology Demonstration (ATD-1) Concept of Operations (ConOps), which combines advanced arrival scheduling, controller decision support tools, and aircraft avionics to enable multiple time deconflicted, efficient arrival streams into a high-density terminal airspace. Interval Management (IM) is designed to support the ATD-1 concept by having an "Ownship" (IM-capable) aircraft achieve or maintain a specific time or distance behind a "Target" (preceding) aircraft. The IM software uses IM clearance information and the Ownship data (route of flight, current location, and wind) entered by the flight crew, and the Target aircraft's Automatic Dependent Surveillance-Broadcast state data, to calculate the airspeed necessary for the IM-equipped aircraft to achieve or maintain the assigned spacing goal.

Baxley, Brian T.↗

Evaluation of Flight Deck-Based Interval Management Crew Procedure Feasibility

Air traffic demand is predicted to increase over the next 20 years, creating a need for new technologies and procedures to support this growth in a safe and efficient manner. The National Aeronautics and Space Administration's (NASA) Air Traffic Management Technology Demonstration - 1 (ATD-1) will operationally demonstrate the feasibility of efficient arrival operations combining ground-based and airborne NASA technologies. The integration of these technologies will increase throughput, reduce delay, conserve fuel, and minimize environmental impacts. The ground-based tools include Traffic Management Advisor with Terminal Metering for precise time-based scheduling and Controller Managed Spacing decision support tools for better managing aircraft delay with speed control. The core airborne technology in ATD-1 is Flight deck-based Interval Management (FIM). FIM tools provide pilots with speed commands calculated using information from Automatic Dependent Surveillance - Broadcast. The precise merging and spacing enabled by FIM avionics and flight crew procedures will reduce excess spacing buffers and result in higher terminal throughput. This paper describes a human-in-the-loop experiment designed to assess the acceptability and feasibility of the ATD-1 procedures used in a voice communications environment. This experiment utilized the ATD-1 integrated system of ground-based and airborne technologies. Pilot participants flew a high-fidelity fixed base simulator equipped with an airborne spacing algorithm and a FIM crew interface. Experiment scenarios involved multiple air traffic flows into the Dallas-Fort Worth Terminal Radar Control airspace. Results indicate that the proposed procedures were feasible for use by flight crews in a voice communications environment. The delivery accuracy at the achieve-by point was within +/- five seconds and the delivery precision was less than five seconds. Furthermore, FIM speed commands occurred at a rate of less than one per minute, and pilots found the frequency of the speed commands to be acceptable at all times throughout the experiment scenarios.

Wilson, Sara R.↗

Flight Crew Responses to the Interval Management Alternative Clearances (IMAC) Experiment

Interval Management Alternative Clearances (IMAC) was a human-in-the-loop simulation experiment conducted to explore the efficacy and acceptability of three IM operations: CAPTURE, CROSS, and MAINTAIN. Two weeks of data collection were conducted, with each week using twelve subject pilots and four subject controllers flying ten high-density arrival scenarios into the Denver International Airport. Overall, both the IM operations and procedures were rated very favorably by the flight crew in terms of acceptability, workload, and pilot head down time. However, several critical issues were identified requiring resolution prior to real-world implementation, including the high frequency of IM speed commands, IM speed commands requiring changes to aircraft configuration, and ambiguous IM cockpit displays that did not trigger the intended pilot reaction. The results from this experiment will be used to prepare for a flight test in 2017, and to support the development of an advanced IM concept of operations by the FAA (Federal Aviation Agency) and aviation industry.

Baxley, Brian T.↗

The Space Operations Simulation Center (SOSC) and Closed-loop Hardware Testing for Orion Rendezvous System Design

The Space Operations Simulation Center (SOSC) at the Lockheed Martin (LM) Waterton Campus in Littleton, Colorado is a dynamic test environment focused on Autonomous Rendezvous and Docking (AR&D) development testing and risk reduction activities. The SOSC supports multiple program pursuits and accommodates testing Guidance, Navigation, and Control (GN&C) algorithms for relative navigation, hardware testing and characterization, as well as software and test process development. The SOSC consists of a high bay (60 meters long by 15.2 meters wide by 15.2 meters tall) with dual six degree-of-freedom (6DOF) motion simulators and a single fixed base 6DOF robot. The large testing area (maximum sensor-to-target effective range of 60 meters) allows for large-scale, flight-like simulations of proximity maneuvers and docking events. The facility also has two apertures for access to external extended-range outdoor target test operations. In addition, the facility contains four Mission Operations Centers (MOCs) with connectivity to dual high bay control rooms and a data/video interface room. The high bay is rated at Class 300,000 (. 0.5 m maximum particles/m3) cleanliness and includes orbital lighting simulation capabilities.

D'Souza, Christopher↗

High Resolution Polar Kerr Effect Studies of CsV 3 Sb 5 : Tests for Time-Reversal Symmetry Breaking below the Charge-Order Transition

We report high resolution polar Kerr effect measurements on CsV 3 Sb 5 single crystals in search for signatures of spontaneous time reversal symmetry breaking below the charge order transition at T * = 94 K. Utilizing two different versions of zero-area loop Sagnac interferometers operating at 1550 nm wavelength, each with the fundamental attribute that without a time reversal symmetry breaking sample at its path, the interferometer is perfectly reciprocal, we find no observable Kerr effect to within the noise floor limit of the apparatus at 30 nanoradians. Simultaneous coherent reflection ratio measurements confirm the sharpness of the charge order transition in the same optical volume as the Kerr measurements. At finite magnetic field we observe a sharp onset of a diamagnetic shift in the Kerr signal at T *, which persists down to the lowest temperature without change in trend. Since 1550 nm is an energy that was shown to capture all features of the optical properties of the material that interact with the charge order transition, we are led to conclude that it is highly unlikely that time reversal symmetry is broken in the charge ordered state in CsV 3 Sb 5 .

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

A rose by any other name: Certification seen as process rather than content

Green (1990) believes that the two main factors safeguarding flying from human error are both related to certification and regulation. First is the increasingly proceduralized nature of flying whereby as much as possible is reduced to a rule-based activity. Second is the emphasis placed upon training and competency checking of aircrew in simulators and in the air, both generally and for all particular types of aircraft flown. This leaves, believes Green, other human factors that are relatively unaddressed as yet and which can give rise to human reliability problems. These include: hardware factors and especially pilot/co-pilot relationships; and system factors including fatigue and cost/safety trade-offs. He also, importantly, identifies problems with the integration of the 'electronic crew member' following increased automation. Human reliability failures with artificial intelligence and automation, due to over-reliance on the system fail-safe mechanisms, or to operator under- confidence in the integrity or self-regulating capacity of the system, or to out-of-loop effects, are widely accepted as being due to deficiencies in plant design, planning, management and maintenance more than to 'operator error' - Reason's (1990) latent error or organization pathogens argument. Reliability failures in complex systems are well enough documented to give cause for concern and at least promote a debate on the merits of a full certification program. The purpose of this short paper is to seek out and explore what is valuable in certification, at the least to show that the benefits outweigh the disadvantages and at best to identify positive outcomes perhaps not obtainable in other ways. On both sides of the debate on certification there is general agreement on the need for a better human factors perspective and effort in complex aviation systems design. What is at issue is how this is to be promoted. It is incumbent upon opponents of certification to say how else such promotion be enabled. This is an exploratory and philosophical review, not a focused and specific one, and it will draw upon much that is not firmly in the domain of complex aviation systems.

Wilson, John R.↗

AI-Accelerated Design of Targeted Covalent Inhibitors for SARS-CoV-2

Direct-acting antivirals for the treatment of the COVID-19 pandemic caused by the SARS-CoV-2 virus are needed to complement vaccination efforts. Given the ongoing emergence of new variants, automated experimentation, and active learning based fast workflows for antiviral lead discovery remain critical to our ability to address the pandemic’s evolution in a timely manner. While several such pipelines have been introduced to discover candidates with noncovalent interactions with the main protease (M pro ), here we developed a closed-loop artificial intelligence pipeline to design electrophilic warhead-based covalent candidates. Here, this work introduces a deep learning-assisted automated computational workflow to introduce linkers and an electrophilic “warhead” to design covalent candidates and incorporates cutting-edge experimental techniques for validation. Using this process, promising candidates in the library were screened, and several potential hits were identified and tested experimentally using native mass spectrometry and fluorescence resonance energy transfer (FRET)-based screening assays. We identified four chloroacetamide-based covalent inhibitors of M pro with micromolar affinities (K I of 5.27 μM) using our pipeline. Experimentally resolved binding modes for each compound were determined using room-temperature X-ray crystallography, which is consistent with the predicted poses. The induced conformational changes based on molecular dynamics simulations further suggest that the dynamics may be an important factor to further improve selectivity, thereby effectively lowering KI and reducing toxicity. These results demonstrate the utility of our modular and data-driven approach for potent and selective covalent inhibitor discovery and provide a platform to apply it to other emerging targets.

60 APPLIED LIFE SCIENCES↗

Entanglement entropy of a color flux tube in (2+1)D Yang-Mills theory

We construct a novel flux tube entanglement entropy (FTE 2 ), defined as the excess entanglement entropy relative to the vacuum of a region of color flux stretching between a heavy quark-anti-quark pair in pure gauge Yang-Mills theory. We show that FTE 2 can be expressed in terms of correlators of Polyakov loops, is manifestly gauge-invariant, and therefore free of the ambiguities in computations of the entanglement entropy in gauge theories related to the choice of the center algebra. Employing the replica trick, we compute FTE 2 for SU(2) Yang-Mills theory in (2+1)D and demonstrate that it is finite in the continuum limit. We explore the properties of FTE 2 for a half-slab geometry, which allows us to vary the width and location of the slab, and the extent to which the slab cross-cuts the color flux tube. Following the intuition provided by computations of FTE 2 in (1+1)D, and in a thin string model, we examine the extent to which our FTE 2 results can be interpreted as the sum of an internal color entropy and a vibrational entropy corresponding to the transverse excitations of the string.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2

Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This “knob” domain is analogous to natural cysteine-rich peptides such as knottins in that it is small and stable but can accommodate diverse loops and disulfide bonding patterns. We immunized cattle with SARS-CoV-2 spike and found ultralong CDR H3 antibodies that could neutralize several viral variants at picomolar IC 50 potencies in vitro and could protect from disease in vivo. The independent CDR H3 peptide knobs were expressed and maintained the properties of the parent antibodies. The knob interaction with SARS-CoV-2 spike was revealed by electron microscopy, X-ray crystallography, NMR spectroscopy, and mass spectrometry and established ultralong CDR H3-derived knobs as the smallest known recombinant independent antigen-binding fragment. Unlike other vertebrate antibody fragments, these knobs are not reliant on the immunoglobulin domain and have potential as a new class of therapeutics.

60 APPLIED LIFE SCIENCES↗

Quantifying magnetic field driven lattice distortions in kagome metals at the femto-scale using scanning tunneling microscopy

A wide array of unusual phenomena has recently been uncovered in kagome solids. The charge density wave (CDW) state in the kagome superconductor AV 3 Sb 5 , in particular, intrigued the community; the CDW phase appears to break the time-reversal symmetry despite the absence of spin magnetism, which has been tied to exotic orbital loop currents possibly intertwined with magnetic field tunable crystal distortions. To test this connection, precise determination of the lattice response to an applied magnetic field is crucial but can be challenging at the atomic scale. We establish a scanning tunneling microscopy (STM) based method to study the evolution of the AV 3 Sb 5 atomic structure as a function of magnetic field. The method substantially reduces the errors of typical STM measurements, which are at the order of 1% when measuring an in-plane lattice constant change. Here, we find that the out-of-plane lattice constant of AV 3 Sb 5 remains unchanged (within 10 —6 ) by the application of both in-plane and out-of-plane magnetic fields. We also reveal that the in-plane lattice response to magnetic field is at most at the order of 0.05%. Our experiments provide further constraints on time-reversal symmetry breaking in kagome metals and establish a tool for higher-resolution extraction of the field-lattice coupling at the nanoscale applicable to other quantum materials.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Design and feasibility of a novel program of cervical screening in Nigeria: self-sampled HPV testing paired with visual triage

Background: Accelerated global control of cervical cancer would require primary prevention with human papillomavirus (HPV) vaccination in addition to novel screening program strategies that are simple, inexpensive, and effective. We present the feasibility and outcome of a community-based HPV self-sampled screening program. Methods: In Ile Ife, Nigeria, 9406 women aged 30–49 years collected vaginal self-samples, which were tested for HPV in the local study laboratory using Hybrid Capture-2 (HC2) (Qiagen). HPV-positive women were referred to the colposcopy clinic. Gynecologist colposcopic impression dictated immediate management; biopsies were taken when definite acetowhitening was present to produce a histopathologic reference standard of precancer (and to determine final clinical management). Retrospective linkage to the medical records identified 442 of 9406 women living with HIV (WLWH). Results: With self-sampling, it was possible to screen more than 100 women per day per clinic. Following an audio-visual presentation and in-person instructions, overall acceptability of self-sampling was very high (81.2% women preferring self-sampling over clinician collection). HPV positivity was found in 17.3% of women. Intensive follow-up contributed to 85.9% attendance at the colposcopy clinic. Of those referred, 8.2% were initially treated with thermal ablation and 5.6% with large loop excision of transformation zone (LLETZ). Full visibility of the squamocolumnar junction, necessary for optimal visual triage and ablation, declined from 68.5% at age 30 to 35.4% at age 49. CIN2+ and CIN3+ (CIN- Cervical intraepithelial neoplasia), including five cancers, were identified by histology in 5.9 and 3.2% of the HPV-positive women, respectively (0.9 and 0.5% of the total screening population), leading to additional treatment as indicated. The prevalences of HPV infection and CIN2+ were substantially higher (40.5 and 2.5%, respectively) among WLWH. Colposcopic impression led to over- and under-treatment compared to the histopathology reference standard. Conclusion: A cervical cancer screening program using self-sampled HPV testing, with colposcopic immediate management of women positive for HPV, proved feasible in Nigeria. Based on the collected specimens and images, we are now evaluating the use of a combination of partial HPV typing and automated visual evaluation (AVE) of cervical images to improve the accuracy of the screening program.

59 BASIC BIOLOGICAL SCIENCES↗

Impact of Tiny Fermi Pockets with Extremely High Mobility on the Hall Anomaly in the Kagome Metal CsV 3 ⁢Sb 5

The kagome metal CsV 3 ⁢Sb 5 exhibits an unusual charge-density-wave (CDW) order, where the emergence of loop current order that breaks time-reversal symmetry (TRS) has been proposed. A key feature of this CDW phase is a nonmonotonic Hall effect at low fields, often attributed to TRS breaking. However, its origin remains unclear. Here, we conduct comprehensive magnetotransport measurements on CsV 3 ⁢Sb 5 and, through mobility spectrum analysis, identify the formation of tiny Fermi pockets with extremely high mobility below the CDW transition. Furthermore, electron irradiation experiments reveal that the nonmonotonic Hall effect is significantly suppressed in samples with reduced mobility, despite no substantial change in the electronic structure. In conclusion, these results indicate that the nonmonotonic Hall effect originates from these tiny Fermi pockets with high mobility carriers rather than anomalous Hall mechanisms, providing new insights into understanding the Hall anomaly in this kagome system.

36 MATERIALS SCIENCE↗

Additive Manufacturing of Oxide Dispersion Strengthened Multi Principle Element Alloys for Future Aerospace Applications

Oxide Dispersion Strengthened (ODS) materials have long been of interest for their high temperature applications, and additive manufacturing enables their manufacturing viability. The ODS multi-principle element alloy NiCoCr was prepared using powder metallurgy techniques, additively manufactured, and evaluated for its processingmicrostructure-property relationships. The high temperature foundations of nickel-base superalloys and ODS materials were combined with the manufacturing advantages of 3D printing and the chemical simplicity of NiCoCr to inspire this work, which was divided into powder and printed material assessments. The project was achieved through multiple iterative project loops to assess the processing parameters’ impact on the microstructure and mechanical properties of the feedstock powder and printed material. The powder investigations (Chapter 3) focused on understanding the oxide coating that formed on the metal powder following acoustic mixing. Time of Flight Secondary Ion Mass Spectrometry was used to semi-quantitatively assess the amount of yttrium on the surface of the mixed powders, and indicated that a combination of higher mixing condition energy and moderate mixing time resulted in the most oxide coating on the NiCoCr powder. The results were supported by a qualitative assessment of scanning electron images of coated powder particles. Following mixing, the ODS NiCoCr was consolidated by Laser Powder Bed Fusion. The evaluations of the printed material (Chapter 4) frst considered screening experiments including Archimedes’ density, porosity, and grain size and number metrics from electron backscatter diffraction data. After the ideal additive manufacturing parameters were identifed, both the oxide homogeneity and yield strength were discussed for the idealized printed material. Overall, the project suggests that the combined use of qualitative or semi-quantitative powder surface analysis with Archimedes’ density analyses can be a valid high-throughput technique which can lead to process optimization of Laser Powder Bed Fusion additively manufactured ODS material.

Laura G Wilson↗

Selection of an Alternate Biocide for the ISS Internal Thermal Control System Coolant, Phase 2

The ISS (International Space Station) ITCS (Internal Thermal Control System) includes two internal coolant loops that utilize an aqueous based coolant for heat transfer. A silver salt biocide had previously been utilized as an additive in the coolant formulation to control the growth and proliferation of microorganisms within the coolant loops. Ground-based and in-flight testing demonstrated that the silver salt was rapidly depleted, and did not act as an effective long-term biocide. Efforts to select an optimal alternate biocide for the ITCS coolant application have been underway and are now in the final stages. An extensive evaluation of biocides was conducted to down-select to several candidates for test trials and was reported on previously. Criteria for that down-select included: the need for safe, non-intrusive implementation and operation in a functioning system; the ability to control existing planktonic and biofilm residing microorganisms; a negligible impact on system-wetted materials of construction; and a negligible reactivity with existing coolant additives. Candidate testing to provide data for the selection of an optimal alternate biocide is now in the final stages. That testing has included rapid biocide effectiveness screening using Biolog MT2 plates to determine minimum inhibitory concentration (amount that will inhibit visible growth of microorganisms), time kill studies to determine the exposure time required to completely eliminate organism growth, materials compatibility exposure evaluations, coolant compatibility studies, and bench-top simulated coolant testing. This paper reports the current status of the effort to select an alternate biocide for the ISS ITCS coolant. The results of various test results to select the optimal candidate are presented.

Wilson, Mark E.↗

Comparison of Airborne and Ground-Based Function Allocation Concepts for NextGen Using Human-In-The-Loop Simulations

This paper presents an air/ground functional allocation experiment conducted by the National Aeronautics and Space Administration (NASA) using two human-in-the-Loop simulations to compare airborne and ground-based approaches to NextGen separation assurance. The approaches under investigation are two trajectory-based four-dimensional (4D) concepts; one referred to as "airborne trajectory management with self-separation" (airborne) the other as "ground-based automated separation assurance" (ground-based). In coordinated simulations at NASA's Ames and Langley Research Centers, the primary operational participants -controllers for the ground-based concept and pilots for the airborne concept - manage the same traffic scenario using the two different 4D concepts. The common scenarios are anchored in traffic problems that require a significant increase in airspace capacity - on average, double, and in some local areas, close to 250% over current day levels - in order to enable aircraft to safely and efficiently traverse the test airspace. The simulations vary common independent variables such as traffic density, sequencing and scheduling constraints, and timing of trajectory change events. A set of common metrics is collected to enable a direct comparison of relevant results. The simulations will be conducted in spring 2010. If accepted, this paper will be the first publication of the experimental approach and early results. An initial comparison of safety and efficiency as well as operator acceptability under the two concepts is expected.

Wing, David J.↗