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At least 91 records · Page 5

Development, Application, and Mechanistic Interrogation of a Dual Ni Catalysis Approach to Photoredox-Based C(sp 3 )–C(sp 3 ) Cross-Coupling

The installation of alkyl substituents such as methyl groups is a crucial tactic for the synthesis and diversification of medicinal compounds with improved pharmacological profiles. However, strategies that leverage methyl radical for C(sp 3 ) methylation remain underdeveloped due to the challenge of obtaining cross-selectivity between fleeting aliphatic radicals and alkyl electrophiles. Here, we report the development, application, and interrogation of a conceptually novel mechanistic framework for C(sp 3 )–Me bond formation using two distinct Ni catalysts capable of cross-coupling sterically and electronically diverse alkyl halides (chlorides and bromides) with methyl radical generated photocatalytically from benzaldehyde dimethyl acetal. Furthermore, by modifying the alkyl substituents on the acetal coupling partner, we demonstrate cross-couplings beyond methylation to access an array of 1°–1° and 1°–2° alkyl–alkyl bonds. Experimental and computational mechanistic studies provide support for cooperativity between an in situ-generated (bpy)Ni I (X) catalyst that facilitates XAT and inner-sphere C–C bond formation and a (Tp*)Ni II (acac) cocatalyst that captures methyl radical and engages in concurrent outer-sphere S H 2 coupling.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Redox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems

Abstract Microelectronic devices can directly communicate with biology, as electronic information can be transmitted via redox reactions within biological systems. By engineering biology’s native redox networks, we enable electronic interrogation and control of biological systems at several hierarchical levels: proteins, cells, and cell consortia. First, electro-biofabrication facilitates on-device biological component assembly. Then, electrode-actuated redox data transmission and redox-linked synthetic biology allows programming of enzyme activity and closed-loop electrogenetic control of cellular function. Specifically, horseradish peroxidase is assembled onto interdigitated electrodes where electrode-generated hydrogen peroxide controls its activity. E. coli ’s stress response regulon, oxyRS , is rewired to enable algorithm-based feedback control of gene expression, including an eCRISPR module that switches cell-cell quorum sensing communication from one autoinducer to another—creating an electronically controlled ‘bilingual’ cell. Then, these disparate redox-guided devices are wirelessly connected, enabling real-time communication and user-based control. We suggest these methodologies will help us to better understand and develop sophisticated control for biology.

59 BASIC BIOLOGICAL SCIENCES↗

Laser-based ultrasound interrogation of surface and sub-surface features in advanced manufacturing materials

Abstract Structures formed by advanced manufacturing methods increasingly require nondestructive characterization to enable efficient fabrication and to ensure performance targets are met. This is especially important for aerospace, military, and high precision applications. Surface acoustic waves (SAW) generated by laser-based ultrasound can detect surface and sub-surface defects relevant for a broad range of advanced manufacturing processes, including laser powder bed fusion (LPBF). In particular, an all-optical SAW generation and detection configuration can effectively interrogate laser melt lines. Here we report on scattered acoustic energy from melt lines, voids, and surface features. Sub-surface voids are also characterized using X-ray Computed Tomography (CT). High resolution CT results are presented and compared with SAW measurements. Finite difference simulations inform experimental measurements and analysis.

36 MATERIALS SCIENCE↗

Numerical simulations and experimental measurements of steel and ice impacts on concrete for acoustic interrogation of delaminations in bridge decks

Delaminations in bridge decks typically result from corrosion of the top mat of reinforcing steel, which leads to a localized separation of the concrete cover from the underlying concrete. Because delaminations cannot be detected using visual inspection, rapid, large-area interrogation methods are desired to characterize bridge decks without disruption to traffic, without the subjectivity inherent in existing methods, and with increased inspector safety. To this end, disposable impactors such as water droplets or ice chips can be dropped using automatic dispensers onto concrete surfaces to excite mechanical vibrations while acoustic responses can be recorded using air-coupled microphones. In this work, numerical simulations are used to characterize the flexural response of a model concrete bridge deck subject to both steel and ice impactors, and the results are compared with similar experiments performed in the laboratory on a partially delaminated concrete bridge deck slab. The simulations offer greater understanding of the kinetics of impacts and the responses of materials.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Cas9 interrogates DNA in discrete steps modulated by mismatches and supercoiling

The CRISPR-Cas9 nuclease has been widely repurposed as a molecular and cell biology tool for its ability to programmably target and cleave DNA. Cas9 recognizes its target site by unwinding the DNA double helix and hybridizing a 20-nucleotide section of its associated guide RNA to one DNA strand, forming an R-loop structure. A dynamic and mechanical description of R-loop formation is needed to understand the biophysics of target searching and develop rational approaches for mitigating off-target activity while accounting for the influence of torsional strain in the genome. Here we investigate the dynamics of Cas9 R-loop formation and collapse using rotor bead tracking (RBT), a single-molecule technique that can simultaneously monitor DNA unwinding with base-pair resolution and binding of fluorescently labeled macromolecules in real time. By measuring changes in torque upon unwinding of the double helix, we find that R-loop formation and collapse proceed via a transient discrete intermediate, consistent with DNA:RNA hybridization within an initial seed region. Using systematic measurements of target and off-target sequences under controlled mechanical perturbations, we characterize position-dependent effects of sequence mismatches and show how DNA supercoiling modulates the energy landscape of R-loop formation and dictates access to states competent for stable binding and cleavage. Consistent with this energy landscape model, in bulk experiments we observe promiscuous cleavage under physiological negative supercoiling. The detailed description of DNA interrogation presented here suggests strategies for improving the specificity and kinetics of Cas9 as a genome engineering tool and may inspire expanded applications that exploit sensitivity to DNA supercoiling.

59 BASIC BIOLOGICAL SCIENCES↗

CRISPR-Cas12a bends DNA to destabilize base pairs during target interrogation

RNA-guided endonucleases are involved in processes ranging from adaptive immunity to site-specific transposition and have revolutionized genome editing. CRISPR-Cas9, -Cas12 and related proteins use guide RNAs to recognize ~20-nucleotide target sites within genomic DNA by mechanisms that are not yet fully understood. We used structural and biochemical methods to assess early steps in DNA recognition by Cas12a protein-guide RNA complexes. We show here that Cas12a initiates DNA target recognition by bending DNA to induce transient nucleotide flipping that exposes nucleobases for DNA-RNA hybridization. Cryo-EM structural analysis of a trapped Cas12a–RNA–DNA surveillance complex and fluorescence-based conformational probing show that Cas12a-induced DNA helix destabilization enables target discovery and engagement. This mechanism of initial DNA interrogation resembles that of CRISPR-Cas9 despite distinct evolutionary origins and different RNA-DNA hybridization directionality of these enzyme families. Our findings support a model in which RNA-mediated DNA interference begins with local helix distortion by transient CRISPR-Cas protein binding.

59 BASIC BIOLOGICAL SCIENCES↗

Lifetime-Limited Interrogation of Two Independent 27 Al + Clocks Using Correlation Spectroscopy

Laser decoherence limits the stability of optical clocks by broadening the observable resonance linewidths and adding noise during the dead time between clock probes. Correlation spectroscopy avoids these limitations by measuring correlated atomic transitions between two ensembles, which provides a frequency difference measurement independent of laser noise. Here, we apply this technique to perform stability measurements between two independent clocks based on the 1 S 0 ↔ 3 P 0 transition in 27 Al + . By stabilizing the dominant sources of differential phase noise between the two clocks, we observe coherence between them during synchronous Ramsey interrogations as long as 8 s at a frequency of 1.12 × 10 15 Hz. Here, the observed contrast in the correlation spectroscopy signal is consistent with the 20.6 s 3 P 0 state lifetime and represents a measurement instability of (1.8 ± 0.5) × 10 –16 /√τ/s for averaging periods longer than the probe duration when dead time is negligible.

74 ATOMIC AND MOLECULAR PHYSICS↗

An Artificial Neural Network System for Photon-Based Active Interrogation Applications

Active interrogation (AI) is a promising technique to detect shielded special nuclear materials (SNMs). At the University of Michigan, we are developing a photon-based AI system that uses bremsstrahlung radiation from an electron linear accelerator (linac) as an ionizing source and stilbene organic scintillating detectors for neutron detection. Stilbene scintillators are sensitive to fast neutrons and photons and have excellent pulse shape discrimination (PSD) capabilities. The traditional charge integration (CI) method commonly used for PSD analysis eliminates piled-up pulses and relies on a particle discrimination line to separate neutrons and photons. The presence of the intense photon flux during AI creates a significant number of piled-up events in the stilbene scintillator, thereby posing a great challenge to the traditional CI method. Identifying true single neutron pulses becomes challenging due to the presence of a pile-up cloud and overlapping neutron, photon and pile-up clouds in the PSD analysis. To mitigate the effect of pulse pile up and identify true single neutron pulses from stilbene scintillators, an artificial neural network (ANN) system is developed. The developed ANN system identifies single neutron pulses and neutron-photon combinations from piled-up events. The results obtained from a 252Cf measurement in the presence of the intense photon flux show that the developed ANN system outperforms the traditional CI method. Since many piled-up events lie above the particle discrimination line, they get misclassified as neutrons by the traditional CI method resulting in 25% overestimation of the net neutron count rate during the linac pulse. The overall net neutron count rate (single and restored neutrons) during the linac pulse, estimated by the ANN system is 60% of the ground truth. Energy spectroscopy of the ANN attributed single neutron pulses further provides evidence on the detection of prompt fission neutrons from the 252Cf fission source.

42 ENGINEERING↗

Expected total counts for the Self-Interrogation Neutron Resonance Densitometry measurements of spent nuclear fuel

The Self-Interrogation Neutron Resonance Densitometry (SINRD) is a passive neutron technique that aims at a direct quantification of {sup 239}Pu in spent fuel assemblies by measuring the attenuation of the neutron flux in the energy region close to the 0.3 eV resonance of {sup 239}Pu. The {sup 239}Pu mass is estimated by calculating the SINRD signature, that is the ratio between the neutron counts in the fast energy region and around the 0.3 eV resonance region. The SINRD measurement approach in this study consisted in introducing a small neutron detector in the central guide tube of a PWR 17x17 fuel assembly. In order to measure the neutron flux in the energy regions defined in the SINRD signature, different detector types were used. The response of a bare {sup 238}U fission chamber is considered for the determination of the fast neutron flux, while other thermal-epithermal detectors wrapped in neutron absorbers are envisaged to measure the neutron flux around the resonance region. This paper provides an estimation of the total neutron counts that can be achieved with the detector types proposed for the SINRD measurement. In the first section a set of detectors are evaluated in terms of total neutron counts and sensitivity to the {sup 239}Pu content, in order to identify the optimal measurement configuration for each detector type. Then a study is performed to increase the total neutron counts by increasing the detector size. The study shows that the highest total neutron counts are achieved by using either {sup 3}He or {sup 10}B proportional counters because of the high neutron efficiency of these detectors. However, the calculations indicate that the biggest contribution to the measurement uncertainty is due to the measurement of the fast neutron flux. Finally, similar sensitivity to the {sup 239}Pu content is obtained by using the different detector types for the measurement of the neutron flux close to the resonance region. Therefore, the total neutron counts associated to each detector type will play a major role in the selection of the detector types used for the SINRD measurement. (authors)

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Glass 3D Printing of Microfluidic Pressure Sensor Interrogated by Fiber-Optic Refractometry

This letter reports a novel fused silica microfluidic device with pressure sensing capability that is fabricated by integrated additive and subtractive manufacturing (IASM) method. The sensor consists of a capillary and a 3D printed glass reservoir, where the reservoir volume change under pressure manifests liquid level deviation inside the capillary, thus realizing the conversion between small pressure change into large liquid level variation. Thanks to the design flexibility of this unique IASM method, the proposed microfluidic device is fabricated with liquid-in-glass thermometer configuration, where the reservoir is sealed following a novel 3D printing assisted glass bonding process. And liquid level is interrogated by a fiber-optic sensor based on multimode interference (MMI) effect. This proposed microfluidic device is attractive for chemical and biomedical sensing because it is flexible in design, and maintains good chemical and mechanical stability, and adjustable sensitivity and range.

42 ENGINEERING↗

Fresh Fuel Measurements With the Differential Die-Away Self-Interrogation Instrument

The purpose of the Next Generation Safeguards Initiative (NGSI)-Spent Fuel (SF) Project is to strengthen the technical toolkit of safeguards inspectors and/or other interested parties. Thus the NGSI-SF team is working to achieve the following technical goals more easily and efficiently than in the past using nondestructive assay measurements of spent fuel assemblies: 1) verify the initial enrichment, burnup, and cooling time of facility declaration; 2) detect the diversion or replacement of pins; 3) estimate the plutonium mass; 4) estimate decay heat; and 5) determine the reactivity of spent fuel assemblies. The differential die-away self-interrogation (DDSI) instrument is one instrument that was assessed for years regarding its feasibility for robust, timely verification of spent fuel assemblies. The instrument was recently built and was tested using fresh fuel assemblies in a variety of configurations, including varying enrichment, neutron absorber content, and symmetry. The early die-away method, a multiplication determination method developed in simulation space, was successfully tested on the fresh fuel assembly data and determined multiplication with a root-mean-square (RMS) error of 2.9%. The experimental results were compared with MCNP simulations of the instrument as well. Low multiplication assemblies had agreement with an average RMS error of 0.2% in the singles count rate (i.e., total neutrons detected per second) and 3.4% in the doubles count rates (i.e., neutrons detected in coincidence per second). High-multiplication assemblies had agreement with an average RMS error of 4.1% in the singles and 13.3% in the doubles count rates.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

NLIZE: A Perturbation-Driven Visual Interrogation Tool for Analyzing and Interpreting Natural Language Inference Models

With the recent advances in deep learning, neural network models have obtained state-of-the-art performances for many linguistic tasks in natural language processing. However, this rapid progress also brings enormous challenges. The opaque nature of a neural network model leads to hard-to-debug-systems and difficult-to-interpret mechanisms. Here, we introduce a visualization system that, through a tight yet flexible integration between visualization elements and the underlying model, allows a user to interrogate the model by perturbing the input, internal state, and prediction while observing changes in other parts of the pipeline. We use the natural language inference problem to illustrate how a perturbation-driven paradigm can help domain experts assess the potential limitation of a model, probe its inner states, and interpret and form hypotheses about fundamental model mechanisms such as attention.

97 MATHEMATICS AND COMPUTING↗

Interrogation of spatial metabolome of Ginkgo biloba with high‐resolution matrix‐assisted laser desorption/ionization and laser desorption/ionization mass spectrometry imaging

Abstract Ginkgo biloba is one of the oldest extant seed plants and has a number of unique properties and uses. Numerous efforts have characterized metabolites within the ginkgo plant and their corresponding biosynthesis pathways, but spatio‐chemical information on ginkgo metabolites is lacking. Mass spectrometry (MS) imaging was used to interrogate the spatio‐chemical localization of metabolites with matrix‐assisted laser desorption/ionization and laser desorption/ionization Fourier‐transform ion cyclotron resonance MS across the ginkgo leaf. Flavonoids, particularly unexpected and rare flavonoid cyclodimers, were detected predominately from leaf epidermis; ginkgolic acids and cardanols were observed exclusively in the secretory cavities. A non‐uniform distribution of flavonoids observed between the upper and lower leaf epidermis was verified by liquid chromatography–MS analyses. Other metabolites, such as saccharides, phospholipids, and chlorophylls, occurred mainly in mesophyll cells. Furthermore, organ‐ and tissue‐specific distributions of ginkgolides were revealed in the ginkgo root, young stem, and leaf. The acquired ion images provide important information regarding biosynthesis, transportation, and accumulation of metabolites throughout the ginkgo plant and should help us to understand the physiological roles of several plant secondary metabolites.

Li, Bin↗

High Pressure Sensing and Dynamics Using High Speed Fiber Bragg Grating Interrogation Systems

Fiber Bragg gratings (FBGs) are developing into useful sensing tools for measuring high pressure dynamics in extreme environments under shock loading conditions. Approaches using traditional diode array coupled FBG interrogation systems are often limited to readout speeds in the sub-MHz range. For shock wave physics, required detection speeds approaching 100 MHz are desired. We explore the use of two types of FBG sensing systems that are aimed at applying this technology as embedded high pressure probes for transient shock events. Both approaches measure time resolved spectral shifts in the return light from short (few mm long) uniform FBGs at 1550 nm. In the first approach, we use a fiber coupled spectrometer to demultiplex spectral channels into an array (up to 12) of single element InGaAs photoreceivers. By monitoring the detectors during a shock impact event with high speed recording, we are able to track the pressure induced spectral shifting in FBG down to a time resolution of 20 ns. In the second approach, developed at the Special Technologies Lab, a coherent mode-locked fiber laser is used to illuminate the FBG sensor. After the sensor, wavelength-to-time mapping is accomplished with a chromatic dispersive element, and entire spectra are sampled using a single detector at the modelocked laser repetition rate of 50 MHz. By sampling with a 12 GHz InGaAs detector, direct wavelength mapping in time is recorded, and the pressure induced FBG spectral shift is sampled at 50 MHz. Here, the sensing systems are used to monitor the spectral shifts of FBGs that are immersed into liquid water and shock compressed using explosives. In this configuration, the gratings survive to pressures approaching 50 kbar. We describe both approaches and present the measured spectral shifts from the shock experiments.

fiber Bragg grating sensors, shockwave diagnostics↗

Improved field assessments of chemicals and explosives using high-resolution gamma-ray spectroscopy with a tagged neutron interrogation system

A field-portable tagged neutron interrogation system is being developed for detection of explosives and chemical warfare agents by prompt γ-ray neutron activation analysis. The system combines an associated particle imaging deuterium-tritium neutron generator with a high-purity germanium γ-ray detector. Fine spatial resolution neutron and α detectors enable precise mapping of characteristic γ-ray emission distributions onto high-clarity neutron radiographic images. A narrow coincidence gate associated with each tagged neutron ensures a large signal-to-background ratio, thus significantly improving sensitivity to the chemical compositions of the items being assessed. Recent experimental results recorded from test objects involving mock explosives and other chemicals are presented.

Bucher, Brian [Idaho National Laboratory (INL)]↗

The Effect of the Hyperfine Structure of an Excited Level on the Shape of the Coherent Population Trapping Resonance under Ramsey Interrogation in an Optically Dense Medium

The effect of the hyperfine structure of an excited level on the shape of the coherent population trapping (CPT) resonance under Ramsey interrogation is investigated in media with different optical thicknesses. The shape of the CPT resonance is constructed for optically thin and dense media, and the results are compared. The dependence of the light shift on the optical density of a medium is analyzed. The parameters of the field phases are determined for which the light shift remains constant under fluctuations of the optical thickness of the medium.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Interrogation of Electrochemical Properties of Polymer Electrolyte Thin Films with Interdigitated Electrodes

The ability to characterize bulk and interfacial transport properties of polymer electrolytes is critical to realizing their potential applications in electrochemical energy storage devices. In this paper, we leverage custom microfabricated interdigitated electrode array (IDEs) as a platform to probe ion transport properties of polymer electrolytes films through electrochemical impedance spectroscopy (EIS) measurements. Using poly(ethylene oxide) (PEO) blended with lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) as a model dry polymer electrolyte system, we investigate how geometric parameters of the IDEs influence the quality and analysis of EIS measurements. By focusing on films on the nanometer film thickness (ca. 50 nm), EIS measurements revealed diffusional processes near the electrode/polymer interface that may be difficult to observe with conventional thick films. Moreover, irreversible impedance spectra were observed at elevated temperatures when using IDEs with large electrode metal fractions. These irreversible processes were eliminated through passivation of the IDE with different oxides (SiO 2 , Al 2 O 3 , or TiO 2 ). Ultimately, the ionic conductivity of PEO-LiTFSI electrolytes is confidently determined when appropriate IDE geometries and equivalent circuits are used. Lastly, our work demonstrates the use of IDEs and nanothin polymer electrolytes films as a versatile platform for rapid and efficient interrogation of both bulk and interfacial electrochemical properties.

36 MATERIALS SCIENCE↗

Achieving the hydrogen shot: Interrogating ionomer interfaces

The aim of this study is to enable the hydrogen economy and decarbonize various sectors in our environment that requires less expensive and more durable water electrolyzers, which can meet the Hydrogen-Shot target. The key is to improve the ionomer interfaces in low-temperature water electrolyzers as rapidly as possible, but to do so, it requires a systematic and holistic campaign combining both experiments and theory. In this perspective, we discuss the issues of electrolyzers and needs for translational science. We then present the approach that the Energy EarthShot Research Center: Center for Ionomer-based Water Electrolysis is taking in hopes of inspiring the community with this approach that can be leveraged to multiple problems and technologies.Graphical abstractHighlightsOne way to achieve the Hydrogen-Shot goal of low-cost, clean hydrogen, is advancing research and development on the interfaces of water electrolyzers for both performance and lifetime. The Center for Ionomer-based Water Electrolysis is exploring new techniques and strategies to not only interrogate interfacial phenomena in water electrolyzers to increase efficiency and durability, but also a new paradigm related to synergistic, cojoined experimental and theoretical research.DiscussionCatalyst\ionomer interfaces are complex and not fully understood, but through investigating different interfaces and utilizing digital and physical twins, we can elucidate key mechanisms and understanding.Understanding the dynamic double layer in electrochemical systems that use solid electrolytes is crucial to identifying and mitigating the controlling phenomena to enable increased performance and durability at the technology level.Studying the time and length scales of interfacial changes can be a powerful tool to understand reaction mechanisms and changes in the electrolyzer performance and durability.

Fornaciari, Julie C↗