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At least 19 records

Precision engineering of biological function with large-scale measurements and machine learning

As synthetic biology expands and accelerates into real-world applications, methods for quantitatively and precisely engineering biological function become increasingly relevant. This is particularly true for applications that require programmed sensing to dynamically regulate gene expression in response to stimuli. However, few methods have been described that can engineer biological sensing with any level of quantitative precision. Here, we present two complementary methods for precision engineering of genetic sensors: in silico selection and machine-learning-enabled forward engineering. Both methods use a large-scale genotype-phenotype dataset to identify DNA sequences that encode sensors with quantitatively specified dose response. First, we show that in silico selection can be used to engineer sensors with a wide range of dose-response curves. To demonstrate in silico selection for precise, multi-objective engineering, we simultaneously tune a genetic sensor’s sensitivity (EC 50 ) and saturating output to meet quantitative specifications. In addition, we engineer sensors with inverted dose-response and specified EC 50 . Second, we demonstrate a machine-learning-enabled approach to predictively engineer genetic sensors with mutation combinations that are not present in the large-scale dataset. We show that the interpretable machine learning results can be combined with a biophysical model to engineer sensors with improved inverted dose-response curves.

59 BASIC BIOLOGICAL SCIENCES↗

Fabrication of the Advanced X-ray Astrophysics Facility (AXAF) Optics: A Deterministic, Precision Engineering Approach to Optical Fabrication

The mirror assembly of the AXAF observatory consists of four concentric, confocal, Wolter type 1 telescopes. Each telescope includes two conical grazing incidence mirrors, a paraboloid followed by a hyperboloid. Fabrication of these state-or-the-art optics is now complete, with predicted performance that surpasses the goals of the program. The fabrication of these optics, whose size and requirements exceed those of any previous x-ray mirrors, presented a challenging task requiring the use of precision engineering in many different forms. Virtually all of the equipment used for this effort required precision engineering. Accurate metrology required deterministic support of the mirrors in order to model the gravity distortions which will not be present on orbit. The primary axial instrument, known as the Precision Metrology Station (PMS), was a unique scanning Fizeau interferometer. After metrology was complete, the optics were placed in specially designed Glass Support Fixtures (GSF's) for installation on the Automated Cylindrical Grinder/Polishers (ACG/P's). The GSF's were custom molded for each mirror element to match the shape of the outer surface to minimize distortions of the inner surface. The final performance of the telescope is expected to far exceed the original goals and expectations of the program.

Gordon, T. E.↗

Atomically precise engineering of spin–orbit polarons in a kagome magnetic Weyl semimetal

Atomically precise defect engineering is essential to manipulate the properties of emerging topological quantum materials for practical quantum applications. However, this remains challenging due to the obstacles in modifying the typically complex crystal lattice with atomic precision. Here, we report the atomically precise engineering of the vacancy-localized spin–orbit polarons in a kagome magnetic Weyl semimetal Co 3 Sn 2 S 2 , using scanning tunneling microscope. We achieve the step-by-step repair of the selected vacancies, leading to the formation of artificial sulfur vacancies with elaborate geometry. We find that that the bound states localized around these vacancies undergo a symmetry dependent energy shift towards Fermi level with increasing vacancy size. As the vacancy size increases, the localized magnetic moments of spin–orbit polarons become tunable and eventually become itinerantly negative due to spin–orbit coupling in the kagome flat band. These findings provide a platform for engineering atomic quantum states in topological quantum materials at the atomic scale.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Precision engineering and optomechanics; Proceedings of the Meeting, San Diego, CA, Aug. 10, 11, 1989

Various papers on precision engineering and optomechanics are presented. Individual topics addressed include: performance optimization of an IR sensor optical system, design and development of a rugged airborne scanning optical assembly for a calibrated IR imaging radiometer, numerical method for Cassegrain telescope baffle design, precision alignment of an IR imaging system, optical alignment of a pupil imaging spectrometer, optical alignment equipment and methods for visible and IR imaging meteorological radiometer. Also addressed are: vibration-design aspects of an IR-scanning earth sensor, chopping secondary mirror for the Kuiper Airborne Observatory, advanced flexure suspension systems, subminiature IR detector translation stage, thermal/optical test setup for the Geostationary Operational Environmental Satellite Telescope, design of the GOES telescope secondary mirror mounting.

Vukobratovich, Daniel↗

Molecular Precision Engineering for Efficient Binary Organic Photovoltaics through Energy Level and Fibrillar Structure Modulation

Adjusting the energy levels and fibrillar morphology is paramount to enhancing the power conversion efficiency (PCE) of organic solar cells (OSCs). In the present study, an increase in the open-circuit voltage (VOC) is facilitated through the elongation of the alkyl chain within AQx (namely AQx-8), aiming to decrease the free volume ratio (FVR). This reduction in FVR attenuates electron-phonon coupling, thereby augmenting emission efficiency and diminishing the non-radiative energy loss (ΔEnr). To further refine the energy levels and morphological characteristics, the external undecyl chain of AQx-8 is substituted with a shorter carbon chain and cyclohexane noted for its considerable steric hindrance (AQx-H). Additionally, this alteration significantly mitigates intermolecular aggregation, expands the bandgap, and elevates the lowest unoccupied molecular orbital (LUMO) energy level, culminating in an elevated VOC of 0.923 V in devices based on AQx-H. Morphological analysis reveals that blends based on AQx-H exhibit an enhanced multi-length-scale fibrillar structure, which is conducive to exciton dissociation and charge transport, thereby contributing to a high fill factor (FF) nearing 80%. Consequently, this study reports one of the highest binary PCEs documented, standing at 19.5% (with certification at 19.0%).

14 SOLAR ENERGY↗

Precision Structure Engineering of High-Entropy Oxides under Ambient Conditions

High-entropy oxides (HEOs) have unveiled a unique frontier in the realm of heterogeneous catalysis, taking advantage of the entropic effect and increased complexities to deliver ultrahigh stability and large tuning capability. However, current HEO synthesis mainly relies on high-temperature annealing approaches affording HEOs possessing no or low surface area, inferior active site exposure efficiency, and low controllability over the structure tuning. The grand challenge lies in producing high-quality HEO catalysts with high active site utilization efficiency, which relies on precision structure engineering, preferably under mild conditions. In this work, an in situ lattice engineering approach was developed to afford a supported HEO catalyst under ambient conditions. The HEO compositions (CuCoFeNiMnO x ) were uniformly integrated into the lattice of CeO 2 driven by cavitation-induced nucleation being generated via ultrasonication. The as-afforded catalysts were featured by high surface area, atomically dispersed HEO compositions, active redox properties, abundant oxygen vacancies (O V ), antiagglomeration, and high phase stability under harsh conditions. Compared with the ex situ introduction of HEO on the surface, the in situ method provides dual benefits to maintain the dispersity of HEO via entropic and lattice confinement effects. Engineering the complex HEO within the lattice of fluorite-structured CeO 2 also yields abundant defects (e.g., O V ) and active metal sites with strong reducing properties (e.g., Ce 3+ and Cu + ), which greatly improves the activity of the lattice oxygen and tunability of the adsorption behavior of the guest molecules, especially in the presence of impurities (e.g., water and propane). The catalytic performance of the supported HEO catalyst in oxidative procedures surpasses the pure dense phase HEO as well as the ex situ-generated catalysts. Further, the synthesis approach being developed in this work, together with the fundamental understanding in structure evolution and reaction mechanism, showcases a facile pathway under ambient conditions to generate stable catalysts capable of maintaining structural robustness in high-temperature conditions while delivering enhanced catalytic performance.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Atomically Precise Surface Engineering for Producing Imagers

High-quality surface coatings, and techniques combining the atomic precision of molecular beam epitaxy and atomic layer deposition, to fabricate such high-quality surface coatings are provided. The coatings made in accordance with the techniques set forth by the invention are shown to be capable of forming silicon CCD detectors that demonstrate world record detector quantum efficiency (>50%) in the near and far ultraviolet (155 nm-300 nm). The surface engineering approaches used demonstrate the robustness of detector performance that is obtained by achieving atomic level precision at all steps in the coating fabrication process. As proof of concept, the characterization, materials, and exemplary devices produced are presented along with a comparison to other approaches.

Greer, Frank↗

Precision and manufacturing at the Lawrence Livermore National Laboratory

Precision Engineering is one of the Lawrence Livermore National Laboratory's core strengths. This paper discusses the past and present current technology transfer efforts of LLNL's Precision Engineering program and the Livermore Center for Advanced Manufacturing and Productivity (LCAMP). More than a year ago the Precision Machine Commercialization project embodied several successful methods of transferring high technology from the National Laboratories to industry. Currently, LCAMP has already demonstrated successful technology transfer and is involved in a broad spectrum of current programs. In addition, this paper discusses other technologies ripe for future transition including the Large Optics Diamond Turning Machine.

Saito, Theodore T.↗

Precise Pore Engineering of fcu–Type Y–MOFs for One–Step C 2 H 4 Purification from Ternary C 2 H 6 /C 2 H 4 /C 2 H 2 Mixtures

The purification of C 2 H 4 from C 2 H 6 /C 2 H 4 /C 2 H 2 mixtures is of great significance in the chemical industry for C 2 H 4 production but remains a daunting task. Guided by powerful reticular chemistry principles, herein a systematic study is carried out to engineer pore dimensions and pore functionality of fcu-type Y-based metal–organic frameworks (Y-MOFs) through the construction of a series of eight new structures using linear dicarboxylate linkers with different length and functional groups. This study illustrates how delicate changes in pore size and pore surface chemistry can effectively influence the adsorption preference of C 2 H 6 , C 2 H 4 , and C 2 H 2 by the MOFs. Importantly, clear relations between pore size/pore surface polarity and C 2 adsorption selectivities of this series of MOFs are established. In particular, HIAM-326 built on a linker decorated with trifluoromethoxy group shows notably preferential adsorption of C 2 H 6 and C 2 H 2 over C 2 H 4 , with balanced C 2 H 2 /C 2 H 4 and C 2 H 6 /C 2 H 4 selectivities. Furthermore, this endows the compound with the capability of one-step purification of C 2 H 4 from C 2 H 6 /C 2 H 4 /C 2 H 2 ternary mixtures, which is validated by breakthrough measurements where high purity C 2 H 4 (99.9%+) can be obtained directly from the separation column. Its adsorption thermodynamics and underlying selective adsorption mechanisms are further revealed by ab initio calculations.

36 MATERIALS SCIENCE↗

Alchemical Free Energy Estimators and Molecular Dynamics Engines: Accuracy, Precision, and Reproducibility

The binding free energy between a ligand and its target protein is an essential quantity to know at all stages of the drug discovery pipeline. Assessing this value computationally can offer insight into where efforts should be focused in the pursuit of effective therapeutics to treat a myriad of diseases. In this work, we examine the computation of alchemical relative binding free energies with an eye for assessing reproducibility across popular molecular dynamics packages and free energy estimators. The focus of this work is on 54 ligand transformations from a diverse set of protein targets: MCL1, PTP1B, TYK2, CDK2, and thrombin. These targets are studied with three popular molecular dynamics packages: OpenMM, NAMD2, and NAMD3 alpha. Trajectories collected with these packages are used to compare relative binding free energies calculated with thermodynamic integration and free energy perturbation methods. The resulting binding free energies show good agreement between molecular dynamics packages with an average mean unsigned error between them of 0.50 kcal/mol. The correlation between packages is very good, with the lowest Spearman’s, Pearson’s and Kendall’s tau correlation coefficients being 0.92, 0.91, and 0.76, respectively. Agreement between thermodynamic integration and free energy perturbation is shown to be very good when using ensemble averaging.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Efficient computation of optimal low thrust gravity perturbed orbit transfers

We have developed a new method for solving low-thrust fuel-optimal orbit transfer problems in the vicinity of a large body (planet or asteroid), considering a high-fidelity spherical harmonic gravity model. The algorithm is formulated via the indirect optimization method, leading to a two-point boundary value problem (TPBVP). We make use of a hyperbolic tangent smoothing law for performing continuation on the thrust magnitude to reduce the sharpness of the control switches in early iterations and thus promote convergence. The TPBVP is solved using the method of particular solutions (MPS) shooting method and Picard-Chebyshev numerical integration. Application of Picard-Chebyshev integration affords an avenue for increased efficiency that is not available with step-by-step integrators. We demonstrate that computing the particular solutions with only a low-fidelity force model greatly increases the efficiency of the algorithm while ultimately achieving near machine precision accuracy. A salient feature of the MPS is that it is parallelizable, and thus further speedups are available. It is also shown that, for near Earth orbits and over a small number of en-route revolutions around the Earth, only the zonal perturbation terms are required in the costate equations to obtain a solution that is accurate to machine precision and optimal to engineering precision. The proposed framework can be used for trajectory design around small asteroids and also for orbit debris rendezvous and removal tasks.

Junkins, John L.↗

Precise microbiota engineering at the cellular level

Stably immunized cells and methods of making stably immunized cells are provided. Methods of altering the microbiota of an ecological environment are provided. Methods of modifying target chromosomes are provided. Methods of delivering genetic material to target cells are provided.

59 BASIC BIOLOGICAL SCIENCES↗

Polar Plate Theory for Orthogonal Anisotropy

Laminated fiber-reinforced (or filamentary) composites are used today for their high strength-to-weight and stiffness-to-weight ratios. However, because of the anisotropic behavior of composites, determining the response on a macroscopic scale is challenging. This is particularly evident in the evaluation of the governing differential equations of a circular disk with the fibers of the lamina oriented with rectilinear orthogonality. This includes any situation involving a composite plate of circular geometry in which out-of-plane displacements due to load are desired, such as fastener pull through loading of a composite plate. Current analysis techniques use numerical methods with rectilinear coordinate systems to solve problems with circular geometry. These analyses over predict plate stiffness by 20% and underpredict failure by 70%. Consequently, there is a need to transform classical composite plate theory to a polar coordinate system. In order to better analyze structures with circular geometries the classical composite plate equations are transformed into the plate equations for a rectilinearly anisotropic composite in polar coordinates. A composite plate is typically a laminate of fibers in rectilinear directions. Subsequent to the lay-tip the necessary geometry is cut out of a rectangular plate. In a similar manner, the derivation of the plate equation starts with the fundamental definitions of strain, displacement and curvature and incorporates the material property angular dependence into the equilibrium equations for a differential polar element. In the transformed state, the stiffness coefficients are no longer constant, adding to the complexity of the governing differential equations. This paper discusses the new derivation and evaluation of the plate equations for a circular composite disk with orthogonal rectilinear anisotropy. The resultant new three partial differential equations, which describe the circular anisotropic plate, can be used to evaluate out-of-plane displacements for given load conditions in design of composite Structures. Without the formation of these unique plate equations, design of such structures is not a precise engineering accomplishment due to the lack of precise design tools. Such structures are over designed to compensate and costly tests need to be performed after production to validate safety. Though impossible to present the mathematical solution within the limits of this paper, the application of the newly derived plate equation in its orthotropic form for a balanced symmetric laminate compared favorably with test results and surpassed the results of standard numerical methods. Within the limitations of the problem foundation the predictive model provides a mechanism for establishing out-of-plane deflection levels for a circular composite plate. Future work in this area should include incorporating the circular composite plate equations in Finite Element Models. The new anisotropic polar plate equations call be utilized as a design tool so that the design more accurately meets the requirements, thus taking full advantage of the weight savings of composites. These accomplishments have not previously been presented to the engineering community nor ever proposed to the IAF. Should the proposed paper be accepted for presentation, attendance is assured.

Bailey, Michelle D.↗