Large System Sizes Research Articles

Selection-free precise gene repair using high-capacity adenovector delivery of advanced prime editing systems rescues dystrophin synthesis in DMD muscle cells.

Prime editors have high potential for disease modelling and regenerative medicine efforts including those directed at the muscle-wasting disorder Duchenne muscular dystrophy (DMD). However, the large size and multicomponent nature of prime editing systems pose substantial production and delivery issues. Here, we report that packaging optimized full-length prime editing constructs in adenovector particles (AdVPs) permits installing precise DMD edits in human myogenic cells, namely, myoblasts and mesenchymal stem cells (up to 80% and 64%, respectively). AdVP transductions identified optimized prime-editing reagents capable of correctingDMD reading frames of ∼14% of patient genotypes and restoringdystrophin synthesis and dystrophin-β-dystroglycan linkages in unselected DMD muscle cell populations. AdVPs were equally suitable for correcting DMD iPSC-derived cardiomyocytes and delivering dual prime editors tailored for DMD repair through targeted exon 51 deletion. Moreover, by exploiting the cell cycle-independent AdVP transduction process, we report that 2- and 3-component prime-editing modalities are both most active in cycling than in post-mitotic cells. Finally, we establish that combining AdVP transduction with seamless prime editing allows for stacking chromosomal edits through successive delivery rounds. In conclusion, AdVPs permit versatile investigation of advanced prime editing systems independently of their size and component numbers, which should facilitate their screening and application.

Robustness and Eventual Slow Decay of Bound States of Interacting Microwave Photons in the Google Quantum AI Experiment

Integrable models are characterized by the existence of stable excitations that can propagate indefinitely without decaying. This includes multimagnon bound states in the celebrated XXZ spin-chain model and its integrable Floquet counterpart. A recent Google Quantum AI experiment [A. Morvan , Nature , 240 (2022)] realizing the Floquet model has demonstrated the persistence of such collective excitations even when the integrability is broken: this observation is at odds with the expectation of ergodic dynamics in generic nonintegrable systems. Here, we study the spectrum of the model realized in the experiment using exact diagonalization and physical arguments. We find that isolated bands corresponding to the descendants of the exact bound states of the integrable model are clearly observable in the spectrum for a large range of system sizes. However, our numerical analysis of the localization properties of the eigenstates suggests that the bound states become unstable in the thermodynamic limit. A perturbative estimate of the decay rate agrees with the prediction of an eventual instability for large system sizes. Published by the American Physical Society 2024

Scaling-up VPT2: A feasible route to include anharmonic correction on large molecules

Vibrational analysis plays a crucial role in the investigation of molecular systems. Though methodologies like second-order vibrational perturbation theory (VPT2) have paved the way to more accurate simulations, the computational cost remains a difficult barrier to overcome when the molecular size increases. Building upon recent advances in the identification of resonances, we propose an approach making anharmonic simulations possible for large-size systems, typically unreachable by standard means. This relies on the fact that, often, only portions of the whole spectra are of actual interest. Therefore, the anharmonic corrections can be included selectively on subsets of normal modes directly related to the regions of interest. Starting from the VPT2 equations, we evaluate rigorously and systematically the impact of the truncated anharmonic treatment onto simulations. The limit and feasibility of the reduced-dimensionality approach are detailed, starting on a smaller model system. The methodology is then challenged on the IR absorption and vibrational circular dichroism spectra of an organometallic complex in three different spectral ranges.

Determining Optimal Breakpoints in Urban Power Networks with Genetic Algorithm

The article deals with the issues of optimizing the operating modes of 6-10 kV distribution networks constituted by the large-sized complicated meshed systems. In real time, such networks operate with breaking the circuit to eliminate equalizing currents. The goal of optimizing the networks’ operating modes is to minimize the active power loss. Determining the optimal breakpoints is a complicated discrete task, for which the method of genetic algorithm becomes the most suitable solution

Comparing two entropy functions of a quantum channel

Inspired by a conjecture related to numerical investigations for a quantum channel in a system of large size, we shall study relations between two different entropies of a quantum channel. One of them is defined by Gour and Wilde as the generalization of quantum relative entropy and maximally mixed state. The second one is defined as the difference between the entropy of the Choi state of the quantum channel and a constant number. At first, we show that the latter entropy is an upper boundary of the former entropy. Moreover, we also give a sufficient and necessary condition that the two entropies are equal. That is, if and only if the relative entropy reaches its supremum on the maximal entangled pure state in the former entropy. At last, to study the difference between the two entropies, we expect to find some quantum channels in which their related entropies do not reach their supremum on the maximal entangled pure states for the former entropy. By calculating the two entropies, we find that amplitude-damping channels are desired examples.

Plasmonic photoconductive terahertz focal-plane array with pixel super-resolution

AbstractImaging systems operating in the terahertz part of the electromagnetic spectrum are attractive due to their ability to penetrate many opaque materials and provide unique spectral signatures of various chemicals. However, the use of terahertz imagers in real-world applications has been limited by the slow speed, large size, high cost and complexity of present systems, largely due to the lack of suitable terahertz focal-plane array detectors. Here we report a terahertz focal-plane array that can directly provide the spatial amplitude and phase distributions, along with the ultrafast temporal and spectral information of an imaged object. It consists of a two-dimensional array of ~0.3 million plasmonic photoconductive nanoantennas optimized to rapidly detect broadband terahertz radiation with a high signal-to-noise ratio. We utilized the multispectral nature of the amplitude and phase data captured by these plasmonic nanoantennas to image different objects, including super-resolved etched patterns in a silicon substrate and defects in battery electrodes. By eliminating the need for raster scanning and spatial terahertz modulation, our terahertz focal-plane array offers more than a 1,000-fold increase in the imaging speed compared with the state of the art and potentially suits a broad range of applications in industrial inspection, security screening and medical diagnosis, among others.

Observation of non-local impedance response in a passive electrical circuit

In media with only short-ranged couplings and interactions, it is natural to assume that physical responses must be local. Yet, we discover that this is not necessarily true, even in a system as commonplace as an electric circuit array. This work reports the experimental observation of non-local impedance response in a designed circuit network consisting exclusively of passive elements such as resistors, inductors and capacitors (RLC). Measurements reveal that the removal of boundary connections dramatically affects the two-point impedance between certain distant nodes, even in the absence of any amplification mechanism for the voltage signal. This non-local impedance response is distinct from the reciprocal non-Hermitian skin effect, affecting only selected pairs of nodes even as the circuit Laplacian exhibits universally broken spectral bulk-boundary correspondence. Surprisingly, not only are component parasitic resistances unable to erode the non-local response, but they in fact give rise to novel loss-induced topological modes at sufficiently large system sizes, constituting a new manifestation of the critical non-Hermitian skin effect. Our findings chart a new route towards attaining non-local responses in photonic or electrical metamaterials without involving non-linear, non-local, active or amplificative elements.

Miniature Magnetic Resonance Imaging System for in situ Monitoring of Bacterial Growth and Biofilm Formation.

In situ monitoring of bacterial growth can greatly benefit human healthcare, biomedical research, and hygiene management. Magnetic resonance imaging (MRI) offers two key advantages in tracking bacterial growth: non-invasive monitoring through opaque sample containers and no need for sample pretreatment such as labeling. However, the large size and high cost of conventional MRI systems are the roadblocks for in situ monitoring. Here, we proposed a small, portable MRI system by combining a small permanent magnet and an integrated radio-frequency (RF) electronic chip that excites and reads out nuclear spin motions in a sample, and utilize this small MRI platform for in situ imaging of bacterial growth and biofilm formation. We demonstrate that MRI images taken by the miniature--and thus broadly deployable for in situ work--MRI system provide information on the spatial distribution of bacterial density, and a sequential set of MRI images taken at different times inform the temporal change of the spatial map of bacterial density, showing bacterial growth.

Performance Analysis of RIS-Aided THz Wireless Systems Over α−μ Fading: An Approximate Closed-Form Approach

In this paper, we study a reconfigurable intelligent surfaces (RIS)-assisted Terahertz (THz) wireless systems with hardware impairments, where α-μ small-scale fading is considered for THz links in accordance with a recent measurement campaign. Firstly, we propose an accurate closed-form approximation of a weighted sum of cascaded non-identical α-μ variates based on the Gauss-Laguerre quadrature and a moment-matching method. This approximate approach facilitates analysis of the RIS-THz system over α-μ fading channels. To demonstrate, we derived closed-form expressions of the outage probability (OP), the ergodic capacity (EC), and the energy-efficiency (EE) of the system based on the proposed approximation. Secondly, we approximately characterize the end-to-end channel of the RIS-THz system when the number of RIS elements is large in scenarios with or without the presence of phase-shift errors. Based on this statistical characterization, the closed-form expressions of the OP, the EC, and the EE of the large-size RIS-THz system are obtained. Furthermore, we devise a low-complexity algorithm that jointly optimizes the transmit power and RIS element activation (i.e., ON/OFF RIS) to maximize the EE in the RIS-THz systems. This algorithm adopts an iterative dynamic programming approach for a maximum subarray problem (i.e., Kadane’s algorithm). Finally, simulations are provided to validate the accuracy of the theoretical analysis as well as demonstrate the efficacy of the devised algorithm.

Binary bilayer simulations for partitioning within membranes.

Membrane proteins (MPs) often show preference for one phase over the other, which is characterized by the partition coefficient, Kp. The physical mechanisms underlying Kp have been only inferred indirectly from experiments due to the unavailability of detailed structures and compositions of ordered phases. Molecular dynamics (MD) simulations can complement these details and thus, in principle, provide further insights into the partitioning of MPs between two phases. However, the application of MD has remained difficult due to long time scales required for equilibration and large system size for the phase stability, which have not been fully resolved even in free energy simulations. This chapter describes the recently developed binary bilayer simulation method, where the membrane is composed of two laterally attached membrane patches. The binary bilayer system (BBS) is designed to preserve the lateral packing of both phases in a significantly smaller size compared to that required for macroscopic phase separation. These characteristics are advantageous in partitioning simulations, as the length scale for diffusion across the system can be significantly smaller. Hence the BBS can be efficiently employed in both conventional MD and free energy simulations, though sampling in ordered phases remains difficult due to slow diffusion. Development of efficient lipid swapping methods and its combination with the BBS would be a useful approach for partitioning in coexisting phases.

Phase transitions of the four-state Potts model on the square and the honeycomb lattices

Abstract It is widely believed that the phase transition for the four-state ferromagnetic Potts model on the square lattice is of the pseudo-first order. Specifically, it is expected that first-order phase transition behavior is found on small lattices and that the true nature of second-order phase transition only emerges with large system sizes. It is also intuitively expected that for other geometries, the types of the associated phase transitions should be identical to that of the square lattice. However, after simulating more than 16 million spins for the four-state Pott model, we observe that a feature of first-order phase transition persists on the square lattice. Additionally, a characteristic of second-order phase transition already appears on a small honeycomb lattice. Indications of a pseudo-first-order phase transition were not found in our investigation. This suggests that a thorough analytic calculation may be required to develop a better understanding of the presented results.

Electrochemistry and Electronic Structure of the Deuterium-Grown Boron-Doped Diamond Interfaces

Integration of the first principles quantum mechanical simulations with electrochemistry represents a difficult research area due to the complexity and large size of real systems and computational limitations. On the one hand it is highly desirable to be able to predict electrochemical properties of materials and systems from simulations to limit the money expenditure for experimental work and accelerate applications [1]. On the other hand, utilization of ab-initio simulations to understand the experimentally observed phenomena is also required to embed them into a solid theoretical framework.To fulfill this task, several multiscale approaches are used with the density functional theory (DFT) being fundamental tool for investigation of electronic structure. DFT results can be further extended to build forcefields used in molecular dynamics (MD) [2] for larger scale simulations and non-equillibrium Green's functions for investigations of electronics and spintronics of nanodevices [3]. Semiconductor electrochemistry is one of the most important areas to explore this experiment-theory interface because of the necessity to develop new materials for photovoltaics, photoelectrochemistry, energy storage and conversion. The purpose of the following talk is to show the power of this paradigm by elucidation of the deuterium-grown boron doped diamond (BDD-D) material [4].A brief introduction to the material synthesis, chemical and physical properties is provided exploiting the synchrotron data of X-Ray absorption spectroscopy and X-Ray photoelectron spectroscopy. Then, a strong emphasis is put into merging the (photo)electrochemical data with the first principle results for better understanding of charge transfer phenomena in the nanoscale. Specifically, DFT calculations of projected local density of states clearly show the presence of highly occupied surface states on the (111) plane of BDD-D in contrast to its standard hydrogen-grown counterpart (BDD-H). The resulting surface states are capable of photocurrent generation in the visible light, which is strongly magnified in BDD-D. Moreover, photoelectrochemical measurements evidenced that photocurrents can be positive or negative depending on the bias - despite BDD being a p-type semiconductor. These confirm a profound role of surface states in the semiconductor electrochemistry and capability of photoinduced charge transfer in the modified materials. The proposed picture shines some new light on the commonly established paradigm of band bending as the key factor driving surface properties of the nanodiamond surfaces [5]. Figure. SEM images of a) BDD@D and b) BDD@H; c) grain size distribution among two samples; d) XRD patterns of the diamond films deposited in the D2/CH4 and H2/CH4 gas mixtures. Reflections at 2θ around 44°, 75°, and 91° correspond to the (111), (220), and (311) diamond lattice planes, respectively. Doubling of the reflections is related to the presence of Kα1 and Kα2 wavelengths in the X-ray radiation [4]. Acknowledgements: M.S., M.B., and M.F. thank Helmholtz-Zentrum Berlin (HZB) for the allocation of synchrotron radiation beamtime at HZB (Germany). M.S. gratefully acknowledges the financial support of these studies fromthe Gdansk University of Technology through the DEC-02/2021/IDUB/ II.1/AMERICIUM grant under the Americium – “Excellence Initiative – Research University” program. R.B. acknowledges the funding from the National Science Centre, Poland under the OPUS call in the Weave programme (Project number: 2021/43/I/ST7/03205).

Detection of urban effects on precipitation in the Seoul metropolitan area, South Korea

With growing urban population and expanding urban areas, the importance of understanding urban effects on precipitation keeps increasing. This study attempts to detect urban effects on precipitation in the Seoul Metropolitan Area (SMA), South Korea by analyzing hourly rain gauge data during 2005–2020. Precipitation events are categorized according to 850-hPa wind directions, and the precipitation increase from the upwind to downwind regions are examined for different duration and intensity classes of precipitation events. The downwind precipitation increase is largest in summer (39%), especially in August (64%). The August precipitation is analyzed in detail. Precipitation statistically significantly increases in Seoul for weak winds and 25–50 km downwind of the center of Seoul for westerly winds, and the precipitation increases are largest in the afternoon. For the precipitation increases, the increases in frequency and intensity of precipitation events are responsible. Short-duration and heavy precipitation events associated with small-sized precipitation systems initiated within the SMA are mainly responsible for the precipitation increases. The downwind precipitation increase also occurs for southwesterly, southerly, and southeasterly winds, but the increases are associated with large-sized precipitation systems.

Microstructure evolution under thermo-mechanical operating of rocksalt-structure TiN via neural network potential.

In the process of high temperature service, the mechanical properties of cutting tools decrease sharply due to the peeling of the protective coating. However, the mechanism of such coating failure remains obscure due to the complicated interaction between atomic structure, temperature, and stress. This dynamic evolution nature demands both large system sizes and accurate description on the atomic scale, raising challenges for existing atomic scale calculation methods. Here, we developed a deep neural network (DNN) potential for Ti-N binary systems based on first-principles study datasets to achieve quantum-accurate large-scale atomic simulation. Compared with empirical interatomic potential based on the embedded-atom-method, the developed DNN-potential can accurately predict lattice constants, phonon properties, and mechanical properties under various thermodynamic conditions. Moreover, for the first time, we present the atomic evolution of the fracture behavior of large-scale rocksalt-structure (B1) TiN systems coupled with temperature and stress conditions. Our study validates that interatomic brittle fractures occur when TiN stretches beyond its tensile yield point. Such simulation of coating fracture and cutting behavior based on large-scale atoms can shed new light on understanding the microstructure and mechanical properties of coating tools under extreme operating conditions.

Non-local linear response in anomalous transport

The anomalous heat transport observed in low-dimensional classical systems is associated with super-diffusive spreading of the space–time correlation of the conserved fields in the system. This leads to a non-local linear response relation between the heat current and the local temperature gradient in the non-equilibrium steady state. This relation provides a generalization of Fourier’s law of heat transfer and is characterized by a non-local kernel operator related to the fractional operators describing super-diffusion. The kernel is essentially proportional, in an appropriate hydrodynamic scaling limit, to the time integral of the space–time correlations of local currents in equilibrium. In finite-size systems, the time integral of correlation of microscopic currents at different locations over an infinite duration is independent of the locations. On the other hand, the kernel operator is space-dependent. We demonstrate that the resolution of this apparent puzzle becomes evident when we consider an appropriate combination of the limits of a large system size and a long integration time. Our study shows the importance of properly handling these limits, even when dealing with (open) systems connected to reservoirs. In particular, we reveal how to extract the kernel operator from simulated microscopic current–current correlation data. For two model systems exhibiting anomalous transport, we provide a direct and detailed numerical verifications of the kernel operators.

Electrified externally heated rotary calciner for calcination of cement raw meal

The cement industry can reduce its CO2 emissions by electrifying the calciner. It can avoid emissions from fuel combustion and produce pure CO2 from the calcination reaction (CaCO3 → CaO + CO2) for direct capture. A differential-algebraic equation (DAE) model of an electrified rotary calciner was developed and validated against experimental results. The heat transfer coefficient was around 30 W/(m2K), with the calciner inclined at 15°. This value increased to 80 W/(m2K) by reducing the inclination to 2°. The rotary calciner for producing 1 Mton/yr clinker with an internal diameter of 5 m needs a length of 485 m to reach a calcination degree of 94 %. The large system size suggests that this calciner may not be suitable for full-scale production. However, it can still be used for small-scale green production of calcined limestone.

Orbital-Free Density Functional Theory: An Attractive Electronic Structure Method for Large-Scale First-Principles Simulations.

Kohn-Sham Density Functional Theory (KSDFT) is the most widely used electronic structure method in chemistry, physics, and materials science, with thousands of calculations cited annually. This ubiquity is rooted in the favorable accuracy vs cost balance of KSDFT. Nonetheless, the ambitions and expectations of researchers for use of KSDFT in predictive simulations of large, complicated molecular systems are confronted with an intrinsic computational cost-scaling challenge. Particularly evident in the context of first-principles molecular dynamics, the challenge is the high cost-scaling associated with the computation of the Kohn-Sham orbitals. Orbital-free DFT (OFDFT), as the name suggests, circumvents entirely the explicit use of those orbitals. Without them, the structural and algorithmic complexity of KSDFT simplifies dramatically and near-linear scaling with system size irrespective of system state is achievable. Thus, much larger system sizes and longer simulation time scales (compared to conventional KSDFT) become accessible; hence, new chemical phenomena and new materials can be explored. In this review, we introduce the historical contexts of OFDFT, its theoretical basis, and the challenge of realizing its promise via approximate kinetic energy density functionals (KEDFs). We review recent progress on that challenge for an array of KEDFs, such as one-point, two-point, and machine-learnt, as well as some less explored forms. We emphasize use of exact constraints and the inevitability of design choices. Then, we survey the associated numerical techniques and implemented algorithms specific to OFDFT. We conclude with an illustrative sample of applications to showcase the power of OFDFT in materials science, chemistry, and physics.

High-efficiency static speckle-suppression method based on a combination of beam splitting cavity and liquid-core fiber.

Current static speckle suppression methods have an extremely large system size and unsatisfactory performance. This study proposes a device called beam-splitting cavity (BSC) and establishes a model of speckle suppression based on the combination of BSC and a liquid-core fiber. Subsequently, a passive static speckle suppression system is constructed and the key factors affecting the speckle contrast are studied. Consequently, the speckle contrast was reduced from 30.2% to 3.1%, which is below the human-eye speckle-discrimination limit (<4%). The scheme consists entirely of passive optical elements, which are more applicable to projectors than the traditional static and dynamic speckle-suppression methods.

Forging quantum data: classically defeating an IQP-based quantum test

Recently, quantum computing experiments have for the first time exceeded the capability of classical computers to perform certain computations – a milestone termed "quantum computational advantage." However, verifying the output of the quantum device in these experiments required extremely large classical computations. An exciting next step for demonstrating quantum capability would be to implement tests of quantum computational advantage with efficient classical verification, such that larger system sizes can be tested and verified. One of the first proposals for an efficiently-verifiable test of quantumness consists of hiding a secret classical bitstring inside a circuit of the class IQP, in such a way that samples from the circuit&amp;apos;s output distribution are correlated with the secret. The classical hardness of this protocol has been supported by evidence that directly simulating IQP circuits is hard, but the security of the protocol against other (non-simulating) classical attacks has remained an open question. In this work we demonstrate that the protocol is not secure against classical forgery. We describe a classical algorithm that can not only convince the verifier that the (classical) prover is quantum, but can in fact can extract the secret key underlying a given protocol instance. Furthermore, we show that the key extraction algorithm is efficient in practice for problem sizes of hundreds of qubits. Finally, we provide an implementation of the algorithm, and give the secret vector underlying the "\$25 challenge" posted online by the authors of the original paper.

Emergence of competing electronic states from non-integer nuclear charges

Understanding many-electron phenomena with competing near-degenerate electronic states is of fundamental importance to chemistry and condensed matter physics. One of the most significant challenges for exploring such many-electron phenomena is the necessity for large system sizes in order to realize competing states, far beyond those practical for first-principles methods. Here, we show how allowing non-integer nuclear charges expands the space of computationally tractable electron systems that host competing electronic states. The emergence of competing electronic states from non-integer nuclear charges is exemplified in the simple 2-electron H2 molecule and used to examine the microscopic structure of doped quasi-1D cuprate chains, showing how non-integer nuclear charges can open a window for first-principles calculations of difficult many-electron phenomena.