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At least 325 records · Page 18

The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility in Mycobacterium marinum

ABSTRACT Isoprenoids are a diverse class of natural products that are essential in all domains of life. Most bacteria synthesize isoprenoids through either the methylerythritol phosphate (MEP) pathway or the mevalonate (MEV) pathway, while a small subset encodes both pathways, including the pathogen Mycobacterium marinum (Mm). It is unclear whether the MEV pathway is functional in Mm, or why Mm encodes seemingly redundant metabolic pathways. Here, we show that the MEP pathway is essential in Mm, while the MEV pathway is dispensable in culture, with the ΔMEV mutant having no growth defect in axenic culture but a competitive growth defect compared to WT Mm. We found that the MEV pathway does not play a role in ex vivo or in vivo acute infection but does play a role in survival of peroxide stress. Metabolite profiling revealed that modulation of the MEV pathway causes compensatory changes in the concentration of MEP intermediates DOXP and CDP-ME, suggesting that the MEV pathway is functional and that the pathways interact at the metabolic level. Finally, the MEV pathway is upregulated early in the shift down to hypoxia, suggesting that it may provide metabolic flexibility to this bacterium. Interestingly, we found that our complemented strains, which vary in copy number of the polyprenyl synthetase idsB2 , responded differently to peroxide and UV stresses, suggesting a role for this gene as a determinant of downstream prenyl phosphate metabolism. Together, these findings suggest that MEV may serve as an anaplerotic pathway to make isoprenoids under stress conditions. IMPORTANCE Organisms from all domains of life utilize isoprenoids to carry out thousands of critical and auxiliary cellular processes, including signaling, maintaining membrane integrity, stress response, and host-pathogen interactions. The common precursor of all isoprenoids is synthesized via one of two biosynthetic pathways. Importantly, some bacteria encode both pathways, including M. marinum . We found that only one pathway is essential in M. marinum , while the nonessential pathway may confer metabolic flexibility to help the bacterium better adapt to various environmental conditions. We also found that the polyprenyl synthetase IdsB2 plays an important role in driving such phenotypes. Further, we demonstrate metabolic interplay between both functional pathways. These insights represent the first characterization of isoprenoid biosynthesis in dual pathway-encoding mycobacteria.

Qabar, Christine M. [Department of Plant and Micro↗

Development of an Optical Library for Coevaporated CdSe x Te 1– x

The conversion efficiency of CdTe solar cells may be improved by bandgap engineering, i.e., changing the bandgap value through the addition of Se in the absorber. The Se alloying enables a short-circuit current density improvement, as it leads to a bandgap energy value decrease. Furthermore, it has been associated with increased minority carrier lifetimes, assuring high open-circuit voltage values. An Se gradient profile control can further optimize the solar cell performance. Thus, an optical model baseline of the CdSe x Te 1–x (CST) compound was developed. Spectroscopic ellipsometry measurements were conducted to accurately extract the optical constants of ten CST layers deposited through coevaporation with x varying from 0 to 1. Using the measured dielectric function spectra from the discrete CST layers with varying x, and considering the composition-induced shift in the critical point energies, an energy-shift model was employed to develop the accurate optical library for the CST compound for any x value to provide data for future modeling and optimization. Furthermore, the library accuracy was validated through optical simulations of the quantum efficiency of a graded CST solar cell using the finite-difference time-domain method by replicating the Se profile in the absorber layer measured through secondary ion mass spectrometry.

14 SOLAR ENERGY↗

How good are learning-based control v.s. model-based control for load shifting? Investigations on a single zone building energy system

Both model predictive control (MPC) and deep reinforcement learning control (DRL) have been presented as a way to approximate the true optimality of a dynamic programming problem, and these two have shown significant operational cost saving potentials for building energy systems. Furthermore, there is still a lack of in-depth quantitative studies on their approximation levels to the true optimality, especially in the building energy domain. To fill in the gap, this paper provides a numerical framework that enables the evaluation of the optimality levels of different controllers for building energy systems. This framework is then used to comprehensively compare the optimal control performance of both MPC and DRL controllers with given computation budgets for a single zone fan coil unit system. Note the optimality is estimated based on a user-specific selection of trade-off weights among energy costs, thermal comfort and control slew rates. Compared with the best optimality we can find through expensive optimization simulations, the best DRL agent can maximally approximate the optimality by 96.54%, which outperforms the best MPC whose optimality level is 90.11%. However, due to the stochasticity, the DRL agent is only expected to approximate the optimality by 90.42%, which is almost equivalent to the best MPC. Except for Proximal Policy Optimization (PPO), all DRL agents can have a better approximation to the optimality than the best MPC, and are expected to have better approximation than the MPC with a prediction horizon of 32 steps (15 min per step). In terms of reducing energy cost and thermal discomfort, MPC can outperform the rule-based control (RBC) by 18.47%–25.44%. DRL can be expected to outperform RBC by 18.95%–25.65% ,and the best DRL control policy can outperform RBC by 20.29%–29.72%. Although the comparison of the optimality level is performed in a perfect setting, e.g., MPC assumes perfect models, and DRL assumes a perfect offline training process and online deployment process, this can shed insight on their capabilities of approximating to the original dynamic programming problem.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Symmetry-dependent ultrafast manipulation of nanoscale magnetic domains

Symmetry is a powerful concept in physics, but its applicability to far-from-equilibrium states is still being understood. Recent attention has focused on how far-from-equilibrium states lead to spontaneous symmetry breaking. Conversely, ultrafast optical pumping can be used to drastically change the energy landscape and quench the magnetic order parameter in magnetic systems. Here, we find a distinct symmetry-dependent ultrafast behaviour by use of ultrafast x-ray scattering from magnetic patterns with varying degrees of isotropic and anisotropic symmetry. After pumping with an optical laser, the scattered intensity reveals a radial shift exclusive to the isotropic component and exhibits a faster recovery time from quenching for the anisotropic component. These features arise even when both symmetry components are concurrently measured, suggesting a correspondence between the excitation and the magnetic order symmetry. Our results underline the importance of symmetry as a critical variable to manipulate the magnetic order in the ultrafast regime.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Polarization-controlled volatile ferroelectric and capacitive switching in Sn 2 P 2 S 6

Abstract Smart electronic circuits that support neuromorphic computing on the hardware level necessitate materials with memristive, memcapacitive, and neuromorphic- like functional properties; in short, the electronic response must depend on the voltage history, thus enabling learning algorithms. Here we demonstrate volatile ferroelectric switching of Sn 2 P 2 S 6 at room temperature and see that initial polarization orientation strongly determines the properties of polarization switching. In particular, polarization switching hysteresis is strongly imprinted by the original polarization state, shifting the regions of non-linearity toward zero-bias. As a corollary, polarization switching also enables effective capacitive switching, approaching the sought-after regime of memcapacitance. Landau–Ginzburg–Devonshire simulations demonstrate that one mechanism by which polarization can control the shape of the hysteresis loop is the existence of charged domain walls (DWs) decorating the periphery of the repolarization nucleus. These walls oppose the growth of the switched domain and favor back-switching, thus creating a scenario of controlled volatile ferroelectric switching. Although the measurements were carried out with single crystals, prospectively volatile polarization switching can be tuned by tailoring sample thickness, DW mobility and electric fields, paving way to non-linear dielectric properties for smart electronic circuits.

97 MATHEMATICS AND COMPUTING↗

Attribute-Guided Adversarial Training for Robustness to Natural Perturbations

We report while existing work in robust deep learning has focused on small pixel-level norm-based perturbations, this may not account for perturbations encountered in several real world settings. In many such cases although test data might not be available, broad specifications about the types of perturbations (such as an unknown degree of rotation) may be known. We consider a setup where robustness is expected over an unseen test domain that is not i.i.d. but deviates from the training domain. While this deviation may not be exactly known, its broad characterization is specified a priori, in terms of attributes. We propose an adversarial training approach which learns to generate new samples so as to maximize exposure of the classifier to the attributes-space, without having access to the data from the test domain. Our adversarial training solves a min-max optimization problem, with the inner maximization generating adversarial perturbations, and the outer minimization finding model parameters by optimizing the loss on adversarial perturbations generated from the inner maximization. We demonstrate the applicability of our approach on three types of naturally occurring perturbations --- object-related shifts, geometric transformations, and common image corruptions. Our approach enables deep neural networks to be robust against a wide range of naturally occurring perturbations. We demonstrate the usefulness of the proposed approach by showing the robustness gains of deep neural networks trained using our adversarial training on MNIST, CIFAR-10, and a new variant of the CLEVR dataset.

97 MATHEMATICS AND COMPUTING↗

BRN 3.1 Knockouts Affect the Vestibular, Autonomic, and Circadian Rhythm Responses to 2G Exposure

Our previous studies have demonstrated that 2G exposure via centrifugation significantly attenuated the daily mean and circadian rhythm amplitude of rat body temperature (Tb), heart rate, and activity (Act). In addition, 2G exposure activates neural responses in several vestibular, autonomic, and circadian nuclei. Although we have characterized the effect of 2G on an animal's physiological, neuronal, and behavioral responses, it will be important to understand the underlying neural and physiological mechanisms that mediate those responses. For example, the vestibular responses, proprioceptive feedback, or fluid shifts may be the critical factors that mediate the responses to 2G. As a first step to understand the relative importance of these different response pathways to altered gravitational fields, this study examined the contribution of the vestibular system by utilizing an animal model from molecular biology. Brain 3.1 (Bm 3.1) is a POU domain homeobox gene involved in the normal development of the vestibular and auditory system. Brn 3.1 deletion results in a loss of hair cells in the otoliths, semicircular canals, and cochlea. As a result mice with a Brn 3.1 deletion do not have a functioning vestibular or auditory system. The BRN 3.1 knockout mouse could be a very useful animal model for isolating the role of the vestibular system in mediating the physiological responses to 2G exposure. Therefore, this study compared the effect of 2G exposure via centrifugation between Brn 3.1 knockout (KO) versus Wildtype (W) mice.

Murakami, D. M.↗

Coupled Fluid-Structure Interaction Analysis of Solid Rocket Motor with Flexible Inhibitors

Flexible inhibitors are generally used in solid rocket motors (SRMs) as a means to control the burning of propellant. Vortices generated by the flow of propellant around the flexible inhibitors have been identified as a driving source of instabilities that can lead to thrust oscillations in launch vehicles. Potential coupling between the SRM thrust oscillations and structural vibration modes is an important risk factor in launch vehicle design. As a means to predict and better understand these phenomena, a multidisciplinary simulation capability that couples the NASA production CFD code, Loci/CHEM, with CFDRC's structural finite element code, CoBi, has been developed. This capability is crucial to the development of NASA's new space launch system (SLS). This paper summarizes the efforts in applying the coupled software to demonstrate and investigate fluid-structure interaction (FSI) phenomena between pressure waves and flexible inhibitors inside reusable solid rocket motors (RSRMs). The features of the fluid and structural solvers are described in detail, and the coupling methodology and interfacial continuity requirements are then presented in a general Eulerian-Lagrangian framework. The simulations presented herein utilize production level CFD with hybrid RANS/LES turbulence modeling and grid resolution in excess of 80 million cells. The fluid domain in the SRM is discretized using a general mixed polyhedral unstructured mesh, while full 3D shell elements are utilized in the structural domain for the flexible inhibitors. Verifications against analytical solutions for a structural model under a steady uniform pressure condition and under dynamic modal analysis show excellent agreement in terms of displacement distribution and eigenmode frequencies. The preliminary coupled results indicate that due to acoustic coupling, the dynamics of one of the more flexible inhibitors shift from its first modal frequency to the first acoustic frequency of the solid rocket motor. This insight could have profound implications for SRM and flexible inhibitor designs for current and future launch vehicles including SLS.

Yang, H. Q.↗

Timing measurement apparatus

Methods, devices and systems for providing accurate measurements of timing errors using optical techniques are described. An example timing measurement device includes an optical hybrid that receives two optical pulse trains and produces two or more phase shifted optical outputs. The timing measurement device further includes two or more optical filters that receive the outputs of the optical hybrid to produce multiple pulse signals with distinctive frequency bands. The device also includes one or more photodetectors and analog-to-digital converters to receive to produce electrical signals in the digital domain corresponding to the optical outputs of the hybrid. A timing error associated with the optical pulse trains can be determined using the electrical signals in digital domain based on a computed phase difference between a first frequency band signal and a second frequency band signal and a computed frequency difference between the first frequency band signal and the second frequency band.

DeVore, Peter Thomas Setsuda↗

Timing measurement apparatus

Methods, devices and systems for providing accurate measurements of timing errors using optical techniques are described. An example timing measurement device includes an optical hybrid that receives two optical pulse trains and produces two or more phase shifted optical outputs. The timing measurement device further includes two or more optical filters that receive the outputs of the optical hybrid to produce multiple pulse signals with distinctive frequency bands. The device also includes one or more photodetectors and analog-to-digital converters to receive to produce electrical signals in the digital domain corresponding to the optical outputs of the hybrid. A timing error associated with the optical pulse trains can be determined using the electrical signals in digital domain based on a computed phase difference between a first frequency band signal and a second frequency band signal and a computed frequency difference between the first frequency band signal and the second frequency band.

DeVore, Peter Thomas Setsuda↗

Near-field infrared imaging of polar domain walls in Ni 3 TeO 6

Domain walls are leading platforms for the development of ultra-low power switching and memory devices due to their potential to be moved, created, and erased in real time and to mitigate heat flux. Interface vs wavelength size effects unfortunately preclude the measurement of phonons by traditional spectroscopic techniques, so it has been challenging to unravel the primary excitations of the lattice and the symmetries that they represent across these functional interfaces. In this work, we employ synchrotron-based near-field infrared nanospectroscopy to image polar domain walls in multiferroic Ni 3 TeO 6 . This is a unique platform because, in addition to hosting polar and chiral domains that are interlocked with one another, Ni 3 TeO 6 displays both charged and neutral interfaces depending upon the direction allowing the development of structure–property relations. From a local structure and a strain point of view, we find charged walls that are twice as wide as neutral walls as well as strong frequency shifts of vibrational modes across the charged walls. The near-field amplitude drops across the walls as well. We discuss these trends in terms of polarization and chirality as well as phonon lifetimes at functional interfaces.

36 MATERIALS SCIENCE↗

Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase

Abstract The average eukaryotic transfer ribonucleic acid (tRNA) contains 13 post-transcriptional modifications; however, their functional impact is largely unknown. Our understanding of the complex tRNA aminoacylation machinery in metazoans also remains limited. Herein, using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we provide the mechanistic basis for recognition and aminoacylation of fully modified cellular tRNALys3 by human lysyl-tRNA synthetase (h-LysRS). The tRNALys3 anticodon loop modifications S34 (mcm5s2U) and R37 (ms2t6A) play an integral role in recognition by h-LysRS. Modifications in the T-, variable-, and D-loops of tRNALys3 are critical for ordering the metazoan-specific N-terminal domain of LysRS. The two catalytic steps of tRNALys3 aminoacylation are structurally ordered; docking of the 3′-CCA end in the active site cannot proceed until the lysyl–adenylate intermediate is formed and the pyrophosphate byproduct is released. Association of the h-LysRS–tRNALys3 complex with a multi-tRNA synthetase complex-derived peptide shifts the equilibrium toward the 3′-CCA end “docked” conformation and allosterically increases h-LysRS catalytic efficiency. The insights presented here have broad implications for understanding the role of tRNA modifications in protein synthesis, the human aminoacylation machinery, and the growing catalog of metabolic and neurological diseases linked to it.

Devarkar, Swapnil C. (ORCID:000000029271243X)↗

Re-evaluating probable maximum precipitation estimates: sensitivity to transposition domains and storm rotation using modern datasets

This study examines the sensitivity of Probable Maximum Precipitation (PMP) estimates to key methodological decisions embedded in the legacy approach adopted in the U.S. National Weather Service Hydrometeorological Reports No. 51 and No. 52. Although widely used for infrastructure design and risk regulation, fundamental aspects of PMP estimation—such as storm sample size, transposition domain, maximization procedures, and storm rotation—remain poorly constrained and lack formal guidance. Using the Red Rock watershed in Iowa as a case study, and leveraging the 2002–2023 NOAA Analysis of Record for Calibration (AORC) precipitation dataset, we systematically evaluate how each methodological choice, individually and in combination, influences PMP estimates. Our findings demonstrate that PMP is not a fixed physical upper bound but rather a modeling construct shaped heavily by user-defined assumptions. Notably, PMP values derived from modern gridded rainfall datasets can be substantially higher than the legacy estimate used in the original spillway design for Red Rock Dam. Decisions regarding storm sample size, domain extent, climatological window, and particularly storm rotation all contributed to higher PMP estimates. Storm rotation alone—a loosely constrained element in the current PMP practice—can amplify PMP by more than 25%. These results reveal the lack of standardized bounds in current PMP workflows and the need for systematic sensitivity and uncertainty analysis. As PMP estimation shifts toward probabilistic approaches, incorporating physically meaningful storm attributes will be key to developing more transparent, defensible methods for dam safety and climate-resilient infrastructure.

Probable maximum precipitation↗

Frequency domain laser velocimeter signal processor

The features and performance parameters of the frequency domain laser velocimeter signal processor (FDSP) for examining flow phenomena are described. A candidate for replacing the standard signal processor, the FDSP can function receiving bursts of as few as 150 photons in an instantaneous mode or down to a photon resolved regime for an averaging mode. the FDSP has a nonlinear A/D converter and data storage shift registers (high speed recorder group), an elliptic digital filter bank, a controlling microprocessor and frequency and signal gain control circuits (low speed data processing group). The high speed group amplifies, digitizes, identifies and stores burst waveforms and the low speed group identifies the signal frequency within the burst after the signal passes through digital filters. The FDSP can operate in a near-autonomous mode using photon correlation techniques and requires no human intervention for calibration.

Meyers, J. F.↗

Using Fractional Clock-Period Delays in Telemetry Arraying

A set of special digital all-pass finite-impulse- response (FIR) filters produces phase shifts equivalent to delays that equal fractions of the sampling or clock period of a telemetry-data-processing system. These filters have been used to enhance the arraying of telemetry signals that have been received at multiple ground stations from spacecraft (see figure). Somewhat more specifically, these filters have been used to align, in the time domain, the telemetry-data sequences received by the various antennas, in order to maximize the signal-to-noise ratio of the composite telemetric signal obtained by summing the signals received by the antennas. The term arraying in this context denotes a method of enhanced reception of telemetry signals in which several antennas are used to track a single spacecraft. Each antenna receives a signal that comprises a sum of telemetry data plus noise, and these sum data are sent to an arraying combiner for processing. Correlation is the means used to align the set of data from one antenna with that from another antenna. After the data from all the antennas have been aligned in the time domain, they are all added together, sample by sample.

Fort, David↗

Tuning the Double Gyroid Phase Window in Block Copolymers via Polymer Chain Conformation Near the Interface

Block copolymer network morphologies have been proven interesting for applications ranging from mechanical to transport and optical properties. The shape of the polymer chain and its ability to stretch across an interface can be used as handles to target these network morphologies. Here, we show that the double gyroid phase window is broadened when there is a flexible segment near the interface and narrowed when a more constrained segment is placed there by using a series of poly(styrene-b-peptoid) block copolymers in which the polypeptoid block chain conformation can be tuned to adopt either a helical or a coil conformation (NRpe 6 vs Npe 6 ). The double gyroid phase is accessed in both block copolymer series, while the phase boundaries are shifted toward larger polypeptoid volume fractions in the helix-forming PS–(NRpe 6 Nmey) series, due to the more compact helix segment (i.e., the helix segment has the same chain volume as its random coil counterpart but occupies less space). The space-filling difference between the helix and coil segment is further confirmed by the smaller domain spacing of PS–(NRpe 6 Nme 39 ) compared to PS–(Npe 6 Nme 36 ) (13.9 nm vs 14.3 nm) despite the former having a longer polypeptoid block. Furthermore, a broadened double gyroid phase window is accessed in the PS–(Npe 6 Nme y ) series that has a flexible coil segment near the interface. These results demonstrate the possibility of tuning the double gyroid phase in linear block copolymers by chain conformation near the interface alone, highlighting chain conformation as a versatile handle in block copolymer design.

36 MATERIALS SCIENCE↗

All in the timing: epigenetic control of greening

During germination, the emerging seedling relies on a limited supply of energy and nutrients stored within itself and the seed. This often occurs underground in darkness where seedlings undergo skotomorphogenesis, characterized by hypocotyl elongation, reduced root growth, and small closed cotyledons forming an apical hook to protect the shoot apical meristem as the seedling grows though the soil towards sunlight. Such long and pale dark-grown seedlings are commonly referred to as etiolated (from the French étiolier (to make pale)). However, a seedling must eventually find sunlight and make an irreversible shift to photoautotrophic growth (photomorphogenesis or de-etiolation). This leads to a dramatic change in physiology, including reduced hypocotyl elongation, increased root growth, expansion and unfolding of the cotyledons, and the biogenesis of photosynthetic plastids (i.e. chloroplasts). Furthermore, this shift is accompanied by a massive change in gene expression, with about one-third of genes being reprogrammed. A large amount of the transcriptional response is regulated by the plant photoreceptors (phytochromes and cryptochromes) that activate transcriptional networks. Furthermore, this involves the rapid degradation of PHYTOCHROME INTERACTING FACTORS (PIFs), which are basic helix-loop-helix domain-containing transcription factors that repress photomorphogenesis in the dark.

59 BASIC BIOLOGICAL SCIENCES↗

BASS Code Development

The BASS computational aeroacoustic code solves the fully nonlinear Euler equations in the time domain in two-dimensions. The acoustic response of the stator is determined simultaneously for the first three harmonics of the convected vortical gust of the rotor. The spatial mode generation, propagation and decay characteristics are predicted by assuming the acoustic field away from the stator can be represented as a uniform flow with small harmonic perturbations superimposed. The computed field is then decomposed using a joint temporal-spatial transform to determine the wave amplitudes as a function of rotor harmonic and spatial mode order. This report details the following technical aspects of the computations and analysis. 1) the BASS computational technique; 2) the application of periodic time shifted boundary conditions; 3) the linear theory aspects unique to rotor-stator interactions; and 4) the joint spatial-temporal transform. The computational results presented herein are twofold. In each case, the acoustic response of the stator is determined simultaneously for the first three harmonics of the convected vortical gust of the rotor. The fan under consideration here like modern fans is cut-off at +, and propagating acoustic waves are only expected at 2BPF and 3BPF. In the first case, the computations showed excellent agreement with linear theory predictions. The frequency and spatial mode order of acoustic field was computed and found consistent with linear theory. Further, the propagation of the generated modes was also correctly predicted. The upstream going waves propagated from the domain without reflection from the in ow boundary. However, reflections from the out ow boundary were noticed. The amplitude of the reflected wave was approximately 5% of the incident wave. The second set of computations were used to determine the influence of steady loading on the generated noise. Toward this end, the acoustic response was determined with three steady loading conditions: design, low-loading, high-loading. The overall trend showed significant (approximately 10 dB) increases in the generated noise for the highly loaded stator.

Sawyer, Scott↗