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At least 847 records · Page 47

Rhythmic Mechanisms Governing CAM Photosynthesis in Kalanchoe fedtschenkoi : High-Resolution Temporal Transcriptomics

Crassulacean acid metabolism (CAM) is a specialized photosynthetic pathway that enhances water-use efficiency by temporally separating nocturnal CO 2 uptake from daytime decarboxylation and carbon fixation. To uncover the regulatory mechanisms coordinating these temporal dynamics, we generated high-resolution, 48 h time-course transcriptomes for the CAM model Kalanchoe fedtschenkoi under both 12 h/12 h light/dark (LD) cycles and continuous light (LL). A rhythmicity analysis revealed that diel light cues are the dominant driver of transcript oscillations: 16,810 genes (54.3% of annotated genes) exhibited rhythmic expression only under LD, whereas just 399 genes (1.3%) remained rhythmic under LL. A smaller set of 3009 genes (9.7%) oscillated in both conditions, indicating that the intrinsic circadian clock sustains rhythmicity for a limited subset of the transcriptome. A gene co-expression network analysis revealed extensive integration between circadian clock components, core CAM pathway enzymes, and stomatal regulators, defining regulatory modules that coordinate metabolic and physiological timing. Notably, key hub genes associated with post-translational and post-transcriptional regulation, including the E3 ubiquitin ligase HUB2 and several pentatricopeptide repeat (PPR) proteins, act as central nodes in CAM-associated networks. This discovery implicates epigenetic and organellar regulation as previously unrecognized critical tiers of control in CAM. Together, our results support a regulatory model in which CAM rhythmicity is governed by both external light/dark cues and the endogenous circadian clock through multi-level control spanning transcriptional and protein-level regulation. To support community exploration, we also provide an interactive eFP (electronic Fluorescent Pictograph) browser for visualizing time-resolved gene expression profiles.

09 BIOMASS FUELS↗

Why is the Muon g-2 Experiment Shifting Time?

Scientists on Fermilab's Muon g-2 experiment are using a finely tuned clock to precisely measure how fast the muon — a heavy cousin of the electron — precesses, or wobbles, in the presence of a magnetic field. To remove subconscious bias from the experiment's measurements, in March 2018, two Fermilab scientists outside the Muon g-2 collaboration set the clock to a certain frequency. For the period that Muon g-2 is taking data, only they will know that setting. This bias-removal technique is called clock blinding.

47 OTHER INSTRUMENTATION↗

Versatile function of the circadian protein CIPC as a regulator of Erk activation

The CLOCK-interacting protein, Circadian (CIPC), has been identified as an additional negative-feedback regulator of the circadian clock. However, recent study on CIPC knockout mice has shown that CIPC is not critically required for basic circadian clock function, suggesting other unknown biological roles for CIPC. In this study, we focused on the cell cycle dependent nuclear-cytoplasmic shuttling function of CIPC and on identifying its binding proteins. Lys186 and 187 were identified as the essential amino acid residues within the nuclear localization signal (NLS) of CIPC. We identified CIPC-binding proteins such as the multifunctional enzyme CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase), which is a key enzyme for de novo pyrimidine synthesis. Compared to control cells, HEK293 cells overexpressing wild-type CIPC showed suppressed cell proliferation and retardation of cell cycle. We also found that PMA-induced Erk activation was inhibited with expression of wild-type CIPC. In contrast, the NLS mutant of CIPC, which reduced the ability of CIPC to translocate into the nucleus, did not exhibit these biological effects. Since CAD and Erk have significant roles in cell proliferation and cell cycle, CIPC may work as a cell cycle regulator by interacting with these binding proteins. - Highlights: • CIPC is a cell cycle dependent nuclear-cytoplasmic shuttling protein. • K186 and 187are the essential amino acid residues within the NLS of CIPC. • CAD was identified as a novel CIPC-binding protein. • CIPC might regulate the activity and translocation of CAD in the cells.

60 APPLIED LIFE SCIENCES↗

An efficient and portable SIMD algorithm for charge/current deposition in Particle-In-Cell codes

In current computer architectures, data movement (from die to network) is by far the most energy consuming part of an algorithm (≈20pJ/word on-die to ≈10,000 pJ/word on the network). To increase memory locality at the hardware level and reduce energy consumption related to data movement, future exascale computers tend to use many-core processors on each compute nodes that will have a reduced clock speed to allow for efficient cooling. To compensate for frequency decrease, machine vendors are making use of long SIMD instruction registers that are able to process multiple data with one arithmetic operator in one clock cycle. SIMD register length is expected to double every four years. As a consequence, Particle-In-Cell (PIC) codes will have to achieve good vectorization to fully take advantage of these upcoming architectures. In this paper, we present a new algorithm that allows for efficient and portable SIMD vectorization of current/charge deposition routines that are, along with the field gathering routines, among the most time consuming parts of the PIC algorithm. Our new algorithm uses a particular data structure that takes into account memory alignment constraints and avoids gather/scat;ter instructions that can significantly affect vectorization performances on current CPUs. The new algorithm was successfully implemented in the 3D skeleton PIC code PICSAR and tested on Haswell Xeon processors (AVX2-256 bits wide data registers). Results show a factor of ×2 to ×2.5 speed-up in double precision for particle shape factor of orders 1–3. The new algorithm can be applied as is on future KNL (Knights Landing) architectures that will include AVX-512 instruction sets with 512 bits register lengths (8 doubles/16 singles). Program summary Program Title: vec_deposition Program Files doi:http://dx.doi.org/10.17632/nh77fv9k8c.1 Licensing provisions: BSD 3-Clause Programming language: Fortran 90 External routines/libraries: OpenMP > 4.0 Nature of problem: Exascale architectures will have many-core processors per node with long vector data registers capable of performing one single instruction on multiple data during one clock cycle. Data register lengths are expected to double every four years and this pushes for new portable solutions for efficiently vectorizing Particle-In-Cell codes on these future many-core architectures. One of the main hotspot routines of the PIC algorithm is the current/charge deposition for which there is no efficient and portable vector algorithm. Solution method: Here we provide an efficient and portable vector algorithm of current/charge deposition routines that uses a new data structure, which significantly reduces gather/scatter operations. Vectorization is controlled using OpenMP 4.0 compiler directives for vectorization which ensures portability across different architectures. Restrictions: Here we do not provide the full PIC algorithm with an executable but only vector routines for current/charge deposition. These scalar/vector routines can be used as library routines in your 3D Particle-In-Cell code. However, to get the best performances out of vector routines you have to satisfy the two following requirements: (1) Your code should implement particle tiling (as explained in the manuscript) to allow for maximized cache reuse and reduce memory accesses that can hinder vector performances. The routines can be used directly on each particle tile. (2) You should compile your code with a Fortran 90 compiler (e.g Intel, gnu or cray) and provide proper alignment flags and compiler alignment directives (more details in README file).

97 MATHEMATICS AND COMPUTING↗

Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

60 APPLIED LIFE SCIENCES↗

Active laser ranging with frequency transfer using frequency comb

A comb-based active laser ranging scheme is proposed for enhanced distance resolution and a common time standard for the entire system. Three frequency combs with different repetition rates are used as light sources at the two ends where the distance is measured. Pulse positions are determined through asynchronous optical sampling and type II second harmonic generation. Results show that the system achieves a maximum residual of 379.6 nm and a standard deviation of 92.9 nm with 2000 averages over 23.6 m. Moreover, as for the frequency transfer, an atom clock and an adjustable signal generator, synchronized to the atom clock, are used as time standards for the two ends to appraise the frequency deviation introduced by the proposed system. The system achieves a residual fractional deviation of 1.3 × 10{sup −16} for 1 s, allowing precise frequency transfer between the two clocks at the two ends.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DCS - A high flux beamline for time resolved dynamic compression science – Design highlights

The Dynamic Compression Sector (DCS) beamline, a national user facility for time resolved dynamic compression science supported by the National Nuclear Security Administration (NNSA) of the Department of Energy (DOE), has recently completed construction and is being commissioned at Sector 35 of the Advanced Photon Source (APS) at Argonne National Laboratory (ANL). The beamline consists of a First Optics Enclosure (FOE) and four experimental enclosures. A Kirkpatrick–Baez focusing mirror system with 2.2 mrad incident angles in the FOE delivers pink beam to the experimental stations. A refocusing Kirkpatrick–Baez mirror system is situated in each of the two most downstream enclosures. Experiments can be conducted in either white, monochromatic, pink or monochromatic-reflected beam mode in any of the experimental stations by changing the position of two interlocked components in the FOE. The beamline Radiation Safety System (RSS) components have been designed to handle the continuous beam provided by two in-line revolver undulators with periods of 27 and 30 mm, at closed gap, 150 mA beam current, and passing through a power limiting aperture of 1.5 x 1.0 mm{sup 2}. A novel pink beam end station stop [1] is used to stop the continuous and focused pink beam which can achieve a peak heat flux of 105 kW/mm{sup 2}. A new millisecond shutter design [2] is used to deliver a quick pulse of beam to the sample, synchronized with the dynamic event, the microsecond shutter, and the storage ring clock.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Path-accelerated stochastic molecular dynamics: Parallel-in-time integration using path integrals

Massively parallel computer architectures create new opportunities for the performance of long-time scale molecular dynamics (MD) simulations. Here, we introduce the path-accelerated molecular dynamics method that takes advantage of distributed computing to reduce the wall-clock time of MD simulation via parallelization with respect to stochastic MD time steps. The marginal distribution for the time evolution of a system is expressed in terms of a path integral, enabling the use of path sampling techniques to numerically integrate MD trajectories. By parallelizing the evaluation of the path action with respect to time and by initializing the path configurations from a nonequilibrium distribution, the algorithm enables significant speedups in terms of the length of MD trajectories that can be integrated in a given amount of wall-clock time. The method is demonstrated for Brownian dynamics, although it is generalizable to other stochastic equations of motion including open systems. We apply the method to two simple systems, a harmonic oscillator and a Lennard-Jones liquid, and we show that in comparison to the conventional Euler integration scheme for Brownian dynamics, the new method can reduce the wall-clock time for integrating trajectories of a given length by more than three orders of magnitude in the former system and more than two in the latter. This new method for parallelizing MD in the dimension of time can be trivially combined with algorithms for parallelizing the MD force evaluation to achieve further speedup.

Rosa-Raíces, Jorge L.↗

Readout Chip for an L1 Tracking Trigger Using Asynchronous Logic

Adding a silicon based tracker to the level 1 trigger systems for LHC detectors can substantially increase the ability of these systems to find events with patterns of high Pt tracks. This is especially true for high luminosity running where there may be several hundred interactions per crossing. Cooling and mass constraints require that the readout chips have low power and generate little electrical noise. The LHC crossing clock and experiment trigger latency requires that a trigger be able to be made in less than 100 LHC crossings of 25 ns each. One way to minimize power and noise is to use asynchronous logic. We present a readout chip design for both level 1 trigger and event readout that is entirely asynchronous. The only clock used is the LHC crossing clock.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Precision Calculation of Blackbody Radiation Shifts for Optical Frequency Metrology

We show that three group IIIB divalent ions, B{sup +}, Al{sup +}, and In{sup +}, have anomalously small blackbody radiation (BBR) shifts of the ns{sup 2} {sup 1}S{sub 0}-nsnp {sup 3}P{sub 0}{sup o} clock transitions. The fractional BBR shifts for these ions are at least 10 times smaller than those of any other present or proposed optical frequency standards at the same temperature, and are less than 0.3% of the Sr clock shift. We have developed a hybrid configuration-interaction + coupled-cluster method that provides accurate treatment of correlation corrections in such ions and yields a rigorous upper bound on the uncertainty of the final results. We reduce the BBR contribution to the fractional frequency uncertainty of the Al{sup +} clock to 4x10{sup -19} at T=300 K. We also reduce the uncertainties due to this effect at room temperature to 10{sup -18} level for B{sup +} and In{sup +} to facilitate further development of these systems for metrology and quantum sensing.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Parallel-in-time quantum simulation via Page and Wootters quantum time

In the past few decades, researchers have created a veritable zoo of quantum algorithms by drawing inspiration from classical computing, information theory, and even from physical phenomena. Here, we present quantum algorithms for parallel-in-time simulations that are inspired by the Page and Wootters formalism. In this framework, and thus in our algorithms, the classical time variable of quantum mechanics is promoted to the quantum realm by introducing a Hilbert space of “clock” qubits that are then entangled with the “system” qubits. We show that our algorithms can compute temporal properties over 𝑁 different times of many-body systems by only using log⁡(𝑁) clock qubits. As such, we achieve an exponential trade-off between time and spatial complexities. In addition, we rigorously prove that the entanglement created between the system qubits and the clock qubits has operational meaning, as it encodes valuable information about the system’s dynamics. We also provide a circuit depth estimation of all the protocols, showing a running time advantage in computation times over traditional sequential-in-time algorithms. In particular, for the case when the dynamics are determined by the Aubry-Andre model, we present a hybrid method for which our algorithms have a depth that only scales as 𝒪⁡(log⁡(𝑁)⁢𝑛). As a by-product, we can relate the previous schemes to the problem of equilibration of an isolated quantum system, thus indicating that our framework enables a new dimension for studying dynamical properties of many-body systems.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Transgenic Perturbation of the Decarboxylation Phase of Crassulacean Acid Metabolism Alters Physiology and Metabolism But Has Only a Small Effect on Growth

Here, mitochondrial NAD-malic enzyme (ME) and/or cytosolic/plastidic NADP-ME combined with the cytosolic/plastidic pyruvate orthophosphate dikinase (PPDK) catalyze two key steps during light-period malate decarboxylation that underpin secondary CO 2 fixation in some Crassulacean acid metabolism (CAM) species. We report the generation and phenotypic characterization of transgenic RNA interference lines of the obligate CAM species Kalanchoë fedtschenkoi with reduced activities of NAD-ME or PPDK. Transgenic line rNAD-ME1 had 8%, and rPPDK1 had 5% of the wild-type level of activity, and showed dramatic changes in the light/dark cycle of CAM CO 2 fixation. In well-watered conditions, these lines fixed all of their CO 2 in the light; they thus performed C 3 photosynthesis. The alternative malate decarboxylase, NADP-ME, did not appear to compensate for the reduction in NAD-ME, suggesting that NAD-ME was the key decarboxylase for CAM. The activity of other CAM enzymes was reduced as a consequence of knocking out either NAD-ME or PPDK activity, particularly phosphoenolpyruvate carboxylase (PPC) and PPDK in rNAD-ME1 . Furthermore, the circadian clock-controlled phosphorylation of PPC in the dark was reduced in both lines, especially in rNAD-ME1 . This had the consequence that circadian rhythms of PPC phosphorylation, PPC kinase transcript levels and activity, and the classic circadian rhythm of CAM CO 2 fixation were lost, or dampened toward arrhythmia, under constant light and temperature conditions. Surprisingly, oscillations in the transcript abundance of core circadian clock genes also became arrhythmic in the rNAD-ME1 line, suggesting that perturbing CAM in K. fedtschenkoi feeds back to perturb the central circadian clock.

59 BASIC BIOLOGICAL SCIENCES↗

OpenSAMPL: An Open Source Library for Timing and Synchronization Measurements and Analytics

Today's power grid operators are implementing timing and synchronization solutions that provide resilience to Global Navigation Satellite System (GNSS) vulnerabilities. These vendor-specific solutions often come with additional software applications that are designed to monitor that vendor's synchronization performance data. However, resilient timing architectures often resulting in multi-vendor solutions, including approaches that blend terrestrial clocks with space-based subscription services. In such an environment, collecting, analyzing, and visualizing data from a variety of sources within a single platform was heretofore not possible. To address this need, the US Department of Energy's Center for Alternative Synchronization and Timing (CAST) developed OpenSAMPL, the Open Synchronized Analytics and Monitoring Platform, an open-source Python framework for processing, loading, and observing clock measurement data from distributed devices. OpenSAMPL enables the ingestion of diverse clock-probe sources into a scalable time-series database and applies robust analytics. OpenSAMPL currently supports two vendor data pipelines, and will be extended to more in the near future, enabling seamless monitoring of a variety of timing and synchronization devices in a common environment.

Grant, Josh [ORNL] (ORCID:0000000163475060)↗

Network Time Synchronization of the Readout Electronics for a New Radioactive Gas Detection System

In systems with multiple radiation detectors, time synchronization of the data collected from different detectors is essential to reconstruct multi-detector events such as scattering and coincidences. In cases where the number of detectors exceeds the readout channels in a single data acquisition electronics module, multiple modules have to be synchronized, which is traditionally accomplished by distributing clocks and triggers via dedicated connections. To eliminate this added cabling complexity in the case of a new radioactive gas detection system prototype under development at the French Atomic Energy Commission, we implemented time synchronization between multiple XIA Pixie-Net detector readout modules through the existing Ethernet network, based on the IEEE 1588 precision time protocol. The detector system is dedicated to the measurement of radioactive gases at low activity and consists of eight large silicon pixels and two NaI(Tl) detectors, instrumented with a total of three 4-channel Pixie-Net modules. Detecting NaI(Tl)/silicon coincidences will make it possible to identify each radioisotope present in the sample. To allow these identifications at low activities, the Pixie-Net modules must be synchronized to a precision well below the targeted coincidence window of 500-1000 ns. Being equipped with an Ethernet PHY compatible with IEEE 1588 and synchronous Ethernet that outputs a locally generated but system-wide synchronized clock, the Pixie-Net can operate its analog to digital converters and digital processing circuitry with that clock and match time stamps for captured data across the three modules. Depending on the network configuration and synchronization method, the implementation is capable to achieve timing precisions between 300 ns and 200 ps.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Identification of circadian rhythms in Nannochloropsis species using bioluminescence reporter lines

Circadian clocks allow organisms to predict environmental changes caused by the rotation of the Earth. Although circadian rhythms are widespread among different taxa, the core components of circadian oscillators are not conserved and differ between bacteria, plants, animals and fungi. Stramenopiles are a large group of organisms in which circadian rhythms have been only poorly characterized and no clock components have been identified. In this work, we have investigated cell division and molecular rhythms in Nannochloropsis species. In the four strains tested, cell division occurred principally during the night period under diel conditions; however, these rhythms damped within 2–3 days after transfer to constant light. We developed firefly luciferase reporters for the long-term monitoring of in vivo transcriptional rhythms in two Nannochlropsis species, Nannochloropsis oceanica CCMP1779 and Nannochloropsis salina CCMP537. The reporter lines express anticipatory behavior under light/dark cycles and free-running bioluminescence rhythms with periods of ~21–31 h that damped within ~3–4 days under constant light. Using different entrainment regimes, we demonstrate that these rhythms are modulated by a circadian-type oscillator. In addition, the phase of free-running luminescence rhythms can be modulated pharmacologically using a CK1 ε/δ inhibitor, suggesting a role of this kinase in the Nannochloropsis clock. Finally, together with the molecular and genomic tools available for Nannochloropsis species, these reporter lines represent an excellent system for future studies on the molecular mechanisms of stramenopile circadian oscillators.

54 ENVIRONMENTAL SCIENCES↗

Quantifying Stochastic Noise in Cultured Circadian Reporter Cells

We report that stochastic noise at the cellular level has been shown to play a fundamental role in circadian oscillations, influencing how groups of cells entrain to external cues and likely serving as the mechanism by which cell-autonomous rhythms are generated. Despite this importance, few studies have investigated how clock perturbations affect stochastic noise—even as increasing numbers of high-throughput screens categorize how gene knockdowns or small molecules can change clock period and amplitude. This absence is likely due to the difficulty associated with measuring cell-autonomous stochastic noise directly, which currently requires the careful collection and processing of single-cell data. In this study, we show that the damping rate of population-level bioluminescence recordings can serve as an accurate measure of overall stochastic noise, and one that can be applied to future and existing high-throughput circadian screens. Using cell-autonomous fibroblast data, we first show directly that higher noise at the single-cell results in faster damping at the population level. Next, we show that the damping rate of cultured cells can be changed in a dose-dependent fashion by small molecule modulators, and confirm that such a change can be explained by single-cell noise using a mathematical model. We further demonstrate the insights that can be gained by applying our method to a genome-wide siRNA screen, revealing that stochastic noise is altered independently from period, amplitude, and phase. Finally, we hypothesize that the unperturbed clock is highly optimized for robust rhythms, as very few gene perturbations are capable of simultaneously increasing amplitude and lowering stochastic noise. Ultimately, this study demonstrates the importance of considering the effect of circadian perturbations on stochastic noise, particularly with regard to the development of small-molecule circadian therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗

Characterization of Digital Silicon Photomultipliers

Digital Silicon photomultipliers (Digital SiPMs) have become an increasingly viable option for single-photon detection due to their compact size and precise timing and resolution. The following work characterizes the noise performance of a diSiPM designed and tested in-house at Fermilab. The SiPM consists of a 26x32 array of single-photon avalanche diode (SPAD) cells. Through the implementation of a shift register masking circuit, individual SPAD cells can be enabled and disabled at will, allowing for precise detection measurements of single columns (accumulator channels) and cells. The provided circuit design operates on voltage clock pulses and collects data on clock edges allowing for precise tuning of the data collection process by varying the clock frequency, pulse width, and integration period.

Shoemaker, Oliver [U. Chicago (main)]↗