Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding
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Cables are initially qualified for nuclear power plant use for 40 years. As plants extend their operating license to 60 and 80 years, justification for continued cable use must shift to a condition-based approach since it is cost prohibitive to completely replace cables that are likely still capable of performing their design function. The Pacific Northwest National Laboratory (PNNL) Accelerated and Real Time Experimental Nodal Analysis (ARENA) cable motor test bed was used to test the response of a commercial spread spectrum time domain reflectometry (SSTDR) system, a laboratory instrument software-controlled SSTDR, and a vector network analyzer-based frequency domain reflectometry (FDR) system to various cable anomalies. The three instrument systems were able to interrogate cables over a range of frequency bandwidths that can be helpful for human data analysis. Data were subjected to supervised and unsupervised machine learning (ML) analyses to distinguish normal undamaged cable responses from anomalous cable responses. Both supervised and unsupervised ML approaches produced encouraging results with an undamaged/anomalous prediction accuracy from 0.69% to 0.87%. Recommendations for further development and field implementation include increased and more balanced sample sets particularly including more training data.
The third-generation South Pole Telescope camera (SPT-3G) improves upon its predecessor (SPTpol) by an order of magnitude increase in detectors on the focal plane. The technology used to read out and control these detectors, digital frequency-domain multiplexing (DfMUX), is conceptually the same as used for SPTpol, but extended to accommodate more detectors. A nearly 5× expansion in the readout operating bandwidth has enabled the use of this large focal plane, and SPT-3G performance meets the forecasting targets relevant to its science objectives. However, the electrical dynamics of the higher-bandwidth readout differ from predictions based on models of the SPTpol system due to the higher frequencies used and parasitic impedances associated with new cryogenic electronic architecture. To address this, we present an updated derivation for electrical crosstalk in higher-bandwidth DfMUX systems and identify two previously uncharacterized contributions to readout noise, which become dominant at high bias frequency. The updated crosstalk and noise models successfully describe the measured crosstalk and readout noise performance of SPT-3G. These results also suggest specific changes to warm electronics component values, wire-harness properties, and SQUID parameters, to improve the readout system for future experiments using DfMUX, such as the LiteBIRD space telescope.
EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying selection and its fusogenic activity has been maintained for over 40 million years. We determined the structure of the RBD of human EnvP(b)1, which defines structural similarities with extant leukemia viruses, despite little sequence conservation. This structure highlights a common scaffold from which novel receptor binding specificities likely evolved. The evolutionary plasticity of this domain may underlie the diversity of related Envs in circulating viruses.
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Botulinum neurotoxins (BoNTs) are among the deadliest of bacterial toxins. BoNT serotype A and B in particular pose the most serious threat to humans because of their high potency and persistence. To date, there is no effective treatment for late post-exposure therapy of botulism patients. Here, we aim to develop single-domain variable heavy-chain (VHH) antibodies targeting the protease domains (also known as the light chain, LC) of BoNT/A and BoNT/B as antidotes for post-intoxication treatments. Using a combination of X-ray crystallography and biochemical assays, we investigated the structures and inhibition mechanisms of a dozen unique VHHs that recognize four and three non-overlapping epitopes on the LC of BoNT/A and BoNT/B, respectively. We show that the VHHs that inhibit the LC activity occupy the extended substrate-recognition exosites or the cleavage pocket of LC/A or LC/B and thus block substrate binding. Notably, we identified several VHHs that recognize highly conserved epitopes across BoNT/A or BoNT/B subtypes, suggesting that these VHHs exhibit broad subtype efficacy. Further, we identify two novel conformations of the full-length LC/A, that could aid future development of inhibitors against BoNT/A. Our studies lay the foundation for structure-based engineering of protein- or peptide-based BoNT inhibitors with enhanced potencies and cross-subtypes properties.
Cables are initially qualified for nuclear power plant use for 40 years. As plants extend their operating license to 60 and 80 years, continued use of these cables must shift to a performance-based approach since it is cost prohibitive to completely replace cables that are likely still capable of performing their design function. A variety of cable tests are available and are commonly applied during outages when the cables can be taken out of service. Frequency domain reflectometry (FDR) is one of these test methods that is being more broadly accepted and used because it not only detects anomalies along the cable with a low-voltage signal that does not stress the cable insulation, but the technique also locates the anomalies. This supports follow-up local inspection and local repair or partial replacement of a damaged cable segment. Currently, FDR testing is only applied to cables that are taken out of service since the test instrument would be damaged by operational voltages. A related technology that has found some acceptance in the aircraft and rail industry is spread spectrum time domain reflectometry (SSTDR). This technology has been implemented with a custom commercial instrument by LiveWire Innovation Inc. that is designed to operate on live cables up to 1000 volts. One of the main conclusions of a previous effort was that cable reflectometry plots can be difficult for humans to analyze due to baseline noise, low or noisy anomaly response peaks, or large responses from cable ends. Detection of cable anomalies for many of these frequencies and test conditions was challenging for manual analysis. This presented an ideal opportunity for ML analysis to distinguish undamaged cable indications from anomalous cable indications. This research discusses application of machine learning (ML) to reflectometry cable test methods. The goal was to assess feasibility to distinguish undamaged cable reflectometry responses from damaged or anomalous cable reflectometry responses. The assessment considered the 3 instruments, multiple frequency bandwidths from each instrument, multiple cable anomalies and test conditions, and both supervised and unsupervised ML approaches. Although approaches and analysis methods were not identical or directly comparable, both outputs were encouraging. The unsupervised prediction weighted accuracy was assessed by instrument and by frequency. It performed better at high frequencies with the highest prediction accuracy of 0.84 for the higher frequency FDR, 0.79 for the 48-MHz LiveWire SSTDR, and 0.77 for 300-MHz PNNL SSTDR. The initial weighted accuracy average across all frequencies for using supervised ML was 0.56 to 0.68. The supervised analysis was repeated with noisier training data removed resulting in weighted accuracies of 0.69 to 0.87. These weighted accuracies are not directly comparable due to differences in the supervised and unsupervised analysis details but do indicate an encouraging trend. Even with limited and unbalanced data, strong prediction accuracies seem encouraging for further work including more data under a wider range of conditions.
Some problems associated with the design of model-reference adaptive control systems are considered and solutions to these problems are advanced. The stability of the adapted system is a primary consideration in the development of both the time-domain and the frequency-domain design techniques. Consequentially, the use of Liapunov's direct method forms an integral part of the derivation of the design procedures. The application of sensitivity coefficients to the design of model-reference adaptive control systems is considered. An application of the design techniques is also presented.
Bubble domain materials and devices are discussed. One of the materials development goals was a materials system suitable for operation of 16 micrometer period bubble domain devices at 150 kHz over the temperature range -10 C to +60 C. Several material compositions and hard bubble suppression techniques were characterized and the most promising candidates were evaluated in device structures. The technique of pulsed laser stroboscopic microscopy was used to characterize bubble dynamic properties and device performance at 150 kHz. Techniques for large area LPE film growth were developed as a separate task. Device studies included detector optimization, passive replicator design and test and on-chip bridge evaluation. As a technology demonstration an 8 chip memory cell was designed, tested and delivered. The memory elements used in the cell were 10 kilobit serial registers.
A technological and economic assessment is made of providing low data rate service to small earth stations by satellite at Ka-band. Various Frequency Domain Multiple Access (FDMA) and Time Domain Multiple Access (TDMA) scenarios are examined and compared on the basis of cost to the end user. Very small stations (1 to 2 meters in diameter) are found not to be viable alternatives to available terrestrial services. However, medium size (3 to 5 meters) earth stations appear to be very competitive if a minimum throughput of about 1.5 Mbs is maintained. This constrains the use of such terminals to large users and shared use by smaller users. No advantage was found to the use of FDMA. TDMA had a slight advantage from a total system viewpoint and a very significant advantage in the space segment (about 1/3 the required payload weight for an equivalent capacity).
An SU(5) grand unified theory model is used to show how the degeneracy between vacua with different spontaneously broken charge parity can be dynamically lifted by a condensate of heavy fermion pairs. This drives a phase transition to a unique vacuum state with definite charge parity. The transition eliminates the domain walls in a matter antimatter symmetric domain cosmology.
A combination of the time and frequency domains which employs the latter only where the former is inefficient or uncertain is used in Space Shuttle payloads' component mode analyses. Attention is given to the time histories at the launch vehicle/spacecraft interface. The frequency domain allows interface acceleration to be determined without recourse to a new, merged system eigenvalue solution and subsequent 'system modal' responses. The approach has been employed in Galileo spacecraft loads analyses.
The author states various time-domain and frequency-domain conditions pertaining to multivariate strict positive real systems and establishes the relationship between these conditions. Their relationship is clarified by means of a three-tier diagram; each tier represents a set of equivalent conditions successively stronger than the lower tier. The main theorem in the present study can be considered as the positive realness lemma for strictly positive real systems.
An experimental investigation was conducted in the 14- by 22-foot subsonic tunnel at NASA-Langley Research Center to measure the inflow into a scale model helicopter rotor in forward flight. These inflow measurements were acquired utilizing a two-component laser velocimeter, and the data were processed by a frequency-domain processor (FDP). As a subset of the experiment, a time-domain counter processor was utilized simultaneously with an FDP to make a comparison of the two processors possible. The results indicate that the FDP had a marked improvement in processing capability in conditions of low signal-to-noise ratios and had a reduction in the number of erroneous data points acquired. However, the FDP yielded a lower data rate in comparison to the counter when signal-to-noise ratios were high. Comparison of the data sets shows that the FDP consistantly measures velocities which are 0.7 percent higher than those measured by the counter processor.
This work evaluates the feasibility to extend spread spectrum time-domain reflectometry (SSTDR) and frequency domain reflectometry (FDR) electrical cable testing to characterize whether an electrical cable is submerged in water or not and where it may be submerged. Using PNNL’s ARENA cable and motor test bed, shielded and non-shielded electrical cables were evaluated using SSTDR and FDR methods to detect and locate electrical cable exposure to water. Both SSTDR and FDR showed the presence of water with a non-shielded cable. Moisture was only detectable with the shielded cable if the insulation was damaged.
Cables are initially qualified for nuclear power plant use for 40 years. As plants extend their operating license to 60 and 80 years, continued use of these cables must shift to a performance-based approach since it is cost prohibitive to completely replace cables that are likely still capable of performing their design function. A variety of cable tests are available and are commonly applied during outages when the cables can be taken out of service. Frequency domain reflectometry (FDR) is one of these test methods that is being more broadly accepted and used because it not only detects anomalies along the cable with a low-voltage signal that does not stress the cable insulation, but the technique also locates the anomalies. This supports follow-up local inspection and local repair or partial replacement of a damaged cable segment. Currently, FDR testing is only applied to cables that are taken out of service since the test instrument would be damaged by operational voltages.
Not provided.
Multiplexing of radiation detector signals into a single channel significantly reduces the need for a large number of digitizer channels, which reduces the cost and the power consumption of a data acquisition system. We previously demonstrated frequency domain multiplexing by convolution using a prototype system that multiplexed two EJ-309 organic scintillators signals into a single channel. Each detector pulse was converted to a damped sinusoid which was then combined into a single channel. The combined signal was digitized and the original detector signal was recovered from the damped sinusoid by deconvolution. In this paper, we demonstrate the recovery of multiple detector signals that arrive during the same digitized record via a new sequential deconvolution method. Here, when two detectors produce signals in the same digitized record and their pulses do not overlap in time, we found that the charge, arrival time, and particle type can be estimated fairly precisely for the first pulse, but the second pulse exhibits substantial degradation in the precision of the estimated charge and arrival time. When the pulses overlap in time, we demonstrate both theoretically and experimentally that the part of the first pulse that does not overlap with the second can be recovered accurately, so the arrival time and amplitude of the first pulse can be estimated fairly precisely, but not the charge or particle type. None of these quantities can be estimated precisely for the second pulse when the two pulses overlap.