GLiDe: a web-based genome-scale CRISPRi sgRNA design tool for prokaryotes.

Background: CRISPRi screening has become a powerful approach for functional genomic research. However, the off-target effects resulting from the mismatch tolerance between sgRNAs and their intended targets is a primary concern in CRISPRi applications.

Results: We introduce Guide Library Designer (GLiDe), a web-based tool specifically created for the genome-scale design of sgRNA libraries tailored for CRISPRi screening in prokaryotic organisms.

Curvature Dependence of Gravitational-Wave Tests of General Relativity.

High-energy extensions to general relativity modify the Einstein-Hilbert action with higher-order curvature corrections and theory-specific coupling constants. The order of these corrections imprints a universal curvature dependence on observations while the coupling constant controls the deviation strength. In this Letter, we leverage the theory-independent expectation that modifications to the action of a given order in spacetime curvature (Riemann tensor and contractions) lead to observational deviations that scale with the system length scale to a corresponding power.

Bootstrap Principle for the Spectrum and Scattering of Strings.

We show that the Veneziano amplitude of string theory is the unique solution to an analytically solvable bootstrap problem. Uniqueness follows from two assumptions: faster than power-law falloff in high-energy scattering and the existence of some infinite sequence in momentum transfer at which higher-spin exchanges cancel. The string amplitude-including the mass spectrum-is an output of this bootstrap.

Detecting a Long-Lived False Vacuum with Quantum Quenches.

Distinguishing whether a system supports alternate low-energy (locally stable) states-stable (true vacuum) versus metastable (false vacuum)-by direct observation can be difficult when the lifetime of the state is very long but otherwise unknown. Here we demonstrate, in a tractable model system, that there are physical phenomena on much shorter timescales that can diagnose the difference. Specifically, we study the time evolution of the magnetization following a quench in the tilted quantum Ising model, and show that its magnitude spectrum is an effective diagnostic.

The coherent structure of the energy cascade in isotropic turbulence.

The energy cascade, i.e. the transfer of kinetic energy from large-scale to small-scale flow motions, has been the cornerstone of turbulence theories and models since the 1940s.

Enhanced sensitivity via non-Hermitian topology.

Sensors are indispensable tools of modern life that are ubiquitously used in diverse settings ranging from smartphones and autonomous vehicles to the healthcare industry and space technology. By interfacing multiple sensors that collectively interact with the signal to be measured, one can go beyond the signal-to-noise ratios (SNR) attainable by the individual constituting elements. Such techniques have also been implemented in the quantum regime, where a linear increase in the SNR has been achieved via using entangled states.

Spectroscopic Signatures of Phonon Character in Molecular Electron Spin Relaxation.

Spin-lattice relaxation constitutes a key challenge for the development of quantum technologies, as it destroys superpositions in molecular quantum bits (qubits) and magnetic memory in single molecule magnets (SMMs). Gaining mechanistic insight into the spin relaxation process has proven challenging owing to a lack of spectroscopic observables and contradictions among theoretical models. Here, we use pulse electron paramagnetic resonance (EPR) to profile changes in spin relaxation rates ( ) as a function of both temperature and magnetic field orientation, forming a two-dimensional data matrix.

A novel concept of an acoustic ultrasound wearable for early detection of implant failure.

Mechanical failure of medical implants, especially in orthopedic poses a significant burden to the patients and healthcare system. The majority of the implant failures are diagnosed at very late stages and are of mechanical causes. This makes the diagnosis and screening of implant failure very challenging.

Days-old zebrafish rapidly learn to recognize threatening agents through noradrenergic and forebrain circuits.

Animals need to rapidly learn to recognize and avoid predators. This ability may be especially important for young animals due to their increased vulnerability. It is unknown whether, and how, nascent vertebrates are capable of such rapid learning.

A General Nonbonded Force Field Based on Accurate Quantum Mechanics Calculations for Elements H-La and Hf-Rn.

Noncovalent interactions (NCI) play a central role in numerous physical, chemical, and biological phenomena. An accurate description of NCI is the key to success for any theoretical study in such areas. Although quantum mechanics (QM) methods such as dispersion-corrected density functional theory are sufficiently accurate, their applications are practical only for <300 atoms and <100 ps of simulation time.

Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.

Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression.

Entanglement-Enabled Advantage for Learning a Bosonic Random Displacement Channel.

We show that quantum entanglement can provide an exponential advantage in learning properties of a bosonic continuous-variable (CV) system. The task we consider is estimating a probabilistic mixture of displacement operators acting on n bosonic modes, called a random displacement channel. We prove that if the n modes are not entangled with an ancillary quantum memory, then the channel must be sampled a number of times exponential in n in order to estimate its characteristic function to reasonable precision; this lower bound on sample complexity applies even if the channel inputs and measurements performed on channel outputs are chosen adaptively or have unrestricted energy.

Pressure estimation of ultra-high frequency ultrasound using gas vesicles.

Acoustic microscopy uses ultra-high frequency (UHF) ultrasound transducers over 80 MHz to perform high-resolution imaging. The pressure output of these transducers is unknown, as commercial calibrated hydrophones can measure pressure for transducers with frequencies only up to 80 MHz. This study used gas vesicle nanostructures (GVs) that collapse at 571 kPa to estimate the pressure of UHF transducers at 40, 80, 200, and 375 MHz.

Multifunctional Porous Soft Composites for Bimodal Wearable Cardiac Monitors.

Wearable heart monitors are crucial for early diagnosis and treatment of heart diseases in non-clinical settings. However, their long-term applications require skin-interfaced materials that are ultrasoft, breathable, antibacterial, and possess robust, enduring on-skin adherence-features that remain elusive. Here, we have developed multifunctional porous soft composites that meet all these criteria for skin-interfaced bimodal cardiac monitoring.

Collective excitations and low-energy ionization signatures of relativistic particles in silicon detectors.

Solid-state detectors with a low energy threshold have several applications, including searches of non-relativistic halo dark-matter particles with sub-GeV masses. When searching for relativistic, beyond-the-Standard-Model particles with enhanced cross sections for small energy transfers, a small detector with a low energy threshold may have better sensitivity than a larger detector with a higher energy threshold. In this paper, we calculate the low-energy ionization spectrum from high-velocity particles scattering in a dielectric material.

Multiconfigurational Electronic Structure of Nickel Cross-Coupling Catalysts Revealed by X-ray Absorption Spectroscopy.

Ni 2,2'-bipyridine complexes are commonly invoked intermediates in metallaphotoredox cross-coupling reactions. Despite their ubiquity, design principles targeting improved catalytic performance remain underdetermined. A series of Ni(bpy)(Ar)Cl (R = MeOOC, -Bu, R' = CH, CF) complexes were proposed to have multiconfigurational electronic structures on the basis of multiconfigurational/multireference calculations, with significant mixing of Ni → bpy metal-to-ligand charge transfer (MLCT) configurations into the ground-state wave function.

The nitrogenase mechanism: new roles for the dangler?

Dangler sites protruding from a core metallocluster were introduced into the bioinorganic lexicon in 2000 by R.D. Britt and co-workers in an analysis of the tetramanganese oxygen-evolving cluster in photosystem II.

Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance.

Transient exposure to ketamine can trigger lasting changes in behavior and mood. We found that brief ketamine exposure causes long-term suppression of futility-induced passivity in larval zebrafish, reversing the "giving-up" response that normally occurs when swimming fails to cause forward movement. Whole-brain imaging revealed that ketamine hyperactivates the norepinephrine-astroglia circuit responsible for passivity.

On the anatomy of acoustic emission.

Abrupt, local frictional fault failure comprises a displacement that is normally accompanied by acoustic emission (AE)-an impulsive elastic wave broadcast with an amplitude proportional to particle velocity. The aggregate of these displacements is the basic fault motion. In laboratory shear experiments, the examination of a sequence of laboratory earthquakes includes continuous measurements of fault motion and the associated AE that is broadcast.

Fermionic mean-field theory as a tool for studying spin Hamiltonians.

The Jordan-Wigner transformation permits one to convert spin 1/2 operators into spinless fermion ones, or vice versa. In some cases, it transforms an interacting spin Hamiltonian into a noninteracting fermionic one, which is exactly solved at the mean-field level. Even when the resulting fermionic Hamiltonian is interacting, its mean-field solution can provide surprisingly accurate energies and correlation functions.

Closure equation and higher-order moment relations in the Gauss-Hermite lattice Boltzmann method.

Moment methods are often used to solve transport problems involving the Boltzmann-BGK equation. Because the moment equations are underdetermined, these methods require an additional "closure equation" that relates higher to lower-order moments. Here, we examine the closure equation and higher-order moment relations implicit in the lattice Boltzmann method (LBM) that use Gauss-Hermite quadrature for their discrete velocity sets.

Mitigating Algorithmic Bias in AI-Driven Cardiovascular Imaging for Fairer Diagnostics.

: The research addresses algorithmic bias in deep learning models for cardiovascular risk prediction, focusing on fairness across demographic and socioeconomic groups to mitigate health disparities. It integrates fairness-aware algorithms, susceptible carrier-infected-recovered (SCIR) models, and interpretability frameworks to combine fairness with actionable AI insights supported by robust segmentation and classification metrics. : The research utilised quantitative 3D/4D heart magnetic resonance imaging and tabular datasets from the Cardiac Atlas Project's (CAP) open challenges to explore AI-driven methodologies for mitigating algorithmic bias in cardiac imaging.

Automated non-invasive laser speckle imaging of the chick heart rate and extraembryonic blood vessels and their response to Nifedipine and Amlodipine drugs.

Using our recently developed laser speckle contrast imaging (LSCI) to visualize blood vessels and monitor blood flow noninvasively, we test the utility of the developing chick heart as a functional model for drug screening. To this end, we examined the effects of antihypertensive agents Nifedipine and Amlodipine, belonging to the L-type calcium channel antagonist family, on blood flow visualized noninvasively through the intact shell. Guided by the live view mode, the drugs were injected through the shell and ventral to HH16-19 chick embryos.