LUS+: Extension of the LUS designator concept to differentiate most sequence alleles for 27 STR loci
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Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) is an NMR hyperpolarization technique that relies of the simultaneous exchange of parahydrogen and a to-be-hyperpolarized molecule on the metal center of a polarization-transfer catalyst in a microtesla magnetic field. Until recently, this method has been understood to perform hyperpolarization by establishing level anti-crossings between the nuclear spins of the parahydrogen derived hydrides (acting as a source of hyperpolarization) and those of the substrate. Recently, the application of highly non-intuitive pulse sequences (comprising pulses of microtesla DC fields) was predicted to hyperpolarize nuclear spins more efficiently than the canonical (static-field) SABRE-SHEATH approach. Here we show that by employing a basic “on-off” pulse sequence of rectangular microtesla pulses, it is possible to improve the hyperpolarization efficiency for SABRE-SHEATH of [ 15 N 3 ]metronidazole, an FDA-approved antibiotic (in non-enriched and non-hyperpolarized form) and potential hypoxia sensing molecule. Specifically, we demonstrate that 15N polarization of 18.5 % can be obtained in 80 s of parahydrogen bubbling parahydrogen through a solution containing 20 mM [ 15 N 3 ]metronidazole. In practice, (1.32 ± 0.14)-fold improvements in P 15N was obtained with the pulsed method described here compared to static field technique variant. These results show that pulsed SABRE-SHEATH was successfully applied to 15 N-labeled biologically relevant molecule. Moreover, we also demonstrate that although the pulsed SABRE-SHEATH sequence was designed for polarization transfer from parahydrogen derived hydrides to the metronidazole’s 15 N catalyst-binding site, all three 15 N sites of [ 15 N 3 ]metronidazole attained the hyperpolarized state. This spin-relayed polarization transfer becomes possible due to the 15 N relay network established by their spin-spin J-couplings. The feasibility of the spin-relayed polarization transfer is demonstrated here for the first time for pulsed SABRE-SHEATH (as opposed to the static-field SABRE-SHEATH reported previously) and it paves the way to broad applicability of the technique.
Recent advances in chemical synthesis have created new methodologies for synthesizing sequence-controlled synthetic polymers, but rational design of monomer sequence for desired properties remains challenging. In this work, we synthesize periodic polymers with repetitive segments using a sequence-controlled ring-opening metathesis polymerization (ROMP) method, which draws inspiration from proteins containing repetitive sequence motifs. The repetitive segment architecture is shown to dramatically affect the self-assembly behavior of these materials. In this work, our results show that polymers with identical repetitive sequences assemble into uniform spherical nanoparticles after thermal annealing, whereas copolymers with random placement of segments with different sequences exhibit disordered assemblies without a well-defined morphology. Overall, these results bring a new understanding to the role of periodic repetitive sequences in polymer assembly.
Simulating compound flooding (CF) at the river-ocean interface within large-scale Earth System Models (ESMs) presents significant challenges due to complex interactions between river discharge, storm surge, and tides. This study assesses the comparative advantages of physics-informed and data-driven machine learning (ML) approaches for enhancing local ESM performance. We systematically compare data-driven neural network models (i.e., CNNs, U-Net, Long Short-Term Memory (LSTM), Gated Recurrent Unit), and physics-informed neural network (PINN) models, including vanilla PINN and a finite-difference-based PINN (FD-PINN). Specifically, FD-PINN is introduced to enhance computational efficiency, accelerating vanilla PINNs by ∼6.5 times while improving accuracy. To enhance data-driven model training, a new data-generation approach is developed to sample historical fluvial and coastal flood events, which ensures a robust data set for extreme event prediction. The models are evaluated using a realistic one-dimensional river domain extracted from an ESM's river mesh and the Hurricane Irene event as an independent test case. Results show that FD-PINN achieves accurate predictions with significantly reduced computational costs relative to vanilla PINNs. Among data-driven models, the best overall performance is achieved by a CNN-LSTM hybrid, which balances accuracy and efficiency. While a fully connected CNN (CNN-FC) provides the best accuracy, it incurs high computational cost. Architectures lacking strong temporal modeling tend to underperform on unseen events. These findings highlight the importance of sequence-aware designs for robust generalization. This study reveals the trade-offs between physics-informed and data-driven models and proposes an adaptive hybrid framework for integrating ML into ESMs to enhance local flood simulations.
Dynamic, multi-input gene regulatory networks (GRNs) are ubiquitous in nature. Multilayer CRISPR-based genetic circuits hold great promise for building GRNs akin to those found in naturally occurring biological systems. We develop an approach for creating high-performing activatable promoters that can be assembled into deep, wide, and multi-input CRISPR-activation and -interference (CRISPRa/i) GRNs. By integrating sequence-based design and in vivo screening, we engineer activatable promoters that achieve up to 1,000-fold dynamic range in an Escherichia coli-based cell-free system. These components enable CRISPRa GRNs that are six layers deep and four branches wide. We show the generalizability of the promoter engineering workflow by improving the dynamic range of the light-dependent EL222 optogenetic system from 6-fold to 34-fold. Additionally, high dynamic range promoters enable CRISPRa systems mediated by small molecules and protein–protein interactions. We apply these tools to build input-responsive CRISPRa/i GRNs, including feedback loops, logic gates, multilayer cascades, and dynamic pulse modulators. Our work provides a generalizable approach for the design of high dynamic range activatable promoters and enables classes of gene regulatory functions in cell-free systems.
We present an open-source building performance simulation test bed, the Advanced Controls Test Bed (ACTB), that interfaces high-fidelity Spawn of EnergyPlus building models, with advanced controllers implemented in Python. Additionally, the ACTB leverages the Building Optimization Testing and Alfalfa platforms for managing simulations, providing an external clock, a representational state transfer (REST) application programming interface (API), and key performance indicators for evaluating the effectiveness of control strategies. The REST API allows the development of external controllers programmed in languages such as Python, which provides flexibility and a rich choice of scientific libraries for designing control sequences. We present three test cases based on the U.S. Department of Energy's Reference Small Office Building to demonstrate the ACTB's capabilities: (a) rule-based controls compliant with ASHRAE Guideline 36 control sequences; (b) an economic model predictive control implemented using do-mpc; and (c) a deep Q-network reinforcement learning agent implemented using OpenAI Gym.
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Flight sequence, capsule design, pyrotechnic applications, escape modes, and safety features for Gemini spacecraft
Telescoping of block sequences in factorial models for searching techniques
Mariner Venus 67 power subsystem changes in operation sequences and design tested for Venus flyby mission
The airplane design process and its interfaces with manufacturing and customer operations are documented to be used as criteria for the development of integrated programs for the analysis, design, and testing of aerospace vehicles. Topics cover: design process management, general purpose support requirements, design networks, and technical program elements. Design activity sequences are given for both supersonic and subsonic commercial transports, naval hydrofoils, and military aircraft.
Descriptions of standard post-ejection maneuver sequences for the deployment of IUS, SSUS-A, and SSUS-D upper stages from the space shuttle orbiter are presented. The sequences were designed to satisfy requirements for limiting the damage inflicted on the orbiter by upper-stage exhaust particles, subject to a further requirement for minimizing the impingement of orbiter thruster plumes on the deployed payload. In all cases it was assumed that the orbital maneuvering system engines would be used to apply the orbiter's major separation velocity increment.
Deployable to very large diameters (over 1000 ft), while still remaining compatible with a complete satellite system launch by STS, the cable-catenary antenna comprises: 8 radial deployable boom masts; a deployable hub and feed support center mast; balanced front and back, radial and circumferential catenary cabling for highly accurate (mm) surface control; no interfering cabling in the antenna field; and an RF reflecting mesh supported on the front catenaries. Illustrations show the antenna-satellite system deployed and stowed configurations; the antenna deployment sequence; the design analysis logic; the sizing analysis output, and typical parametric design data.
Spread spectrum code division multiple access (CDMA) allows asynchronous multiple access to a local area network (LAN) with no waiting. The additional bandwidth required by spread spectrum can be accommodated by using a fiber-optic channel and incoherent optical signal processing. New CDMA sequences are designed specifically for optical processing. It is shown that increasing the number of chips per bit, by using optical processing, allows an increase in capacity of a CDMA LAN. An experiment is performed demonstrating the performance of an optical CDMA LAN, operating at 100 Mbd with three users.
Pulsed laser sheet velocimetry yields nonintrusive measurements of velocity vectors across an extended 2-dimensional region of the flow field. The application of optical correlation techniques to the analysis of multiple exposure laser light sheet photographs can reduce and/or simplify the data reduction time and hardware. Here, Matched Spatial Filters (MSF) are used in a pattern recognition system. Usually MSFs are used to identify the assembly line parts. In this application, the MSFs are used to identify the iso-velocity vector contours in the flow. The patterns to be recognized are the recorded particle images in a pulsed laser light sheet photograph. Measurement of the direction of the partical image displacements between exposures yields the velocity vector. The particle image exposure sequence is designed such that the velocity vector direction is determined unambiguously. A global analysis technique is used in comparison to the more common particle tracking algorithms and Young's fringe analysis technique.
Pulsed laser sheet velocimetry yields noninstrusive measurements of velocity vectors across an extended 2-dimensional region of the flow field. The application of optical correlation techniques to the analysis of multiple exposure laser light sheet photographs can reduce and/or simplify the data reduction time and hardware. Here, Matched Spatial Filters (MSF) are used in a pattern recognition system. Usuallay MSFs are used to identify the assembly line parts. In this application, the MSFs are used to identify the iso-velocity vector contours in the flow. The patterns to be recognized are the recorded particle images in a pulsed laser light sheet photograph. Measurement of the direction of the particle image displacements between exposures yields the velocity vector. The particle image exposure sequence is designed such that the velocity vector direction is determined unambiguously. A global analysis technique is used in comparison to the more common particle tracking algorithms and Young's fringe analysis technique.
The interstellar gas experiment (IGE) exposed thin metallic foils in order to collect neutral interstellar particles which penetrate the solar system due to their motion relative to the sun. These atoms were entrapped in the collecting foils along with precipitating magnetospheric ions and with ambient atmospheric atoms. For the entire duration of the LDEF mission, seven of the foils collected particles arriving from seven different directions as seen from the spacecraft. In the mass spectrometric analysis of the trapped noble gas component, we detected the He-3, He-4, Ne-20, and Ne-22 isotopes. In order to infer the isotopic ratios in the interstellar medium from the measured concentrations found in the foil piece, several lines of investigation had to be initiated. The flux of incident noble gas atoms from the ambient atmosphere was estimated by detailed calculations. The contributions proved to be negligible, supporting the experimental evidence. Foil and machine backgrounds for the four isotopes which were measured had to be assessed individually. While this was easy for He-4, spurious foil background of He-3 had to be monitored carefully by analyzing unflown foil pieces. Trapped Ne concentrations are not far above the background. During the flight, a stuck electrical relay precluded the foil-trays from sequencing as designed. Therefore, we could not use the seasonal variation of the direction of the incoming interstellar atoms to make the distinction between interstellar and magnetospheric components of the trapped particles. Instead, we had to try the method of stepwise heating to extract the interstellar component at lower temperatures than we use to extract the magnetospheric component (the interstellars hit the foil with lower energies than most of the magnetospherics). New limiting values for the isotopic composition of the interstellar medium, unavailable yet from any other method of measurement, are emerging from this analysis.
A set of burn profiles was developed to provide bounding jet firing histories for a +vbar breakout during approaches to Space Station Freedom. The delta-v sequences were designed to place the Orbiter on a safe trajectory under worst case conditions and to try to minimize plume impingement on Space Station Freedom structure.