BINA

Base editors are engineered deaminases combined with CRISPR components. These engineered deaminases are designed to target specific sites within DNA or RNA to make a precise change in the molecule. In therapeutics, they hold promise for correcting mutations associated with genetic diseases. However, a key challenge is minimizing unintended edits at off-target sites, which could lead to harmful mutations. Researchers are actively addressing this concern through a variety of optimization efforts that aim to improve the precision of base editors and minimize off-target activity. Here, we examine the various types of off-target activity, and the methods used to evaluate them. Current methods for finding off-target activity focus on identifying similar sequences in the genome or in the transcriptome, assuming the guide RNA misdirects the editor. The main method presented here, that was originally developed to …

Recovery of missing phase information from the intensity correlation is crucial in various applications ranging from astronomy to biology. Interferometry and phase retrieval algorithms are common methods for phase recovery. Here, we present a non-interferometric and iteration-free approach for recovering the phase of the Fourier spectrum. This is implemented in an in-line configuration with a structured illumination and a single-pixel estimation of the intensity correlations. Instead of many temporal measurements, single exposure speckle is used to acquire the complex Fourier spectrum from the intensity correlation. Mapping of the complex Fourier spectrum is demonstrated by discretely varying the frequency of the structured illumination and then extracting the intensity correlations for a set of three phase-shifted structured illuminations at each frequency. Furthermore, the recovered Fourier spectrum is used to …

Mathematical models of voltammetric experiments commonly contain a singular point value for the reversible potential, whereas experimental data for surface-confined redox-active species is often interpreted to contain thermodynamic dispersion, meaning the population of molecules on the electrode possess a distribution of reversible potential values. Large amplitude ramped Fourier Transformed Alternating Current Voltammetry (FTacV), a technique in which a sinusoidal potential-time oscillation is overlaid onto a linear potential-time ramp, is known to provide access to higher order harmonic components that are largely devoid of non-Faradaic current. Initially, a theoretical study reveals that the use of very large amplitude sinusoidal oscillations reduces the apparent effects of thermodynamic dispersion; conversely, frequency can be varied to change the sensitivity of the measurement to kinetic dispersion. Subsequently, FTacV measurements are used to probe a highly thermodynamically dispersed surface-confined ferrocene derivative attached to a glassy carbon electrode, with amplitudes ranging from 25 to 300 mV and low frequency, which minimises the impact of kinetic dispersion. The results from the experimental study validate the theoretical predictions, demonstrating that we can vary the amplitude in FTacV experiments to tune in and out of thermodynamic dispersion.

We generalize the scope of Floquet engineering to include spatially-dependent modulations of an optical system. As an application, we show that we can transform large classes of Hamiltonians into one another by driving them in a time-periodic but spatially non-uniform manner. We propose several experimental realizations in 1D optical lattices, including freeing disordered lattices from Anderson localization, as well as effectively disconnecting all their sites. These techniques straightforwardly extend to more complex classes of systems.

The study of first passage times for diffusing particles reaching target states is foundational in various practical applications, including diffusion-controlled reactions. In this work, we present a bi-scaling theory for the probability density function of first passage times in confined compact processes, applicable to both Euclidean and Fractal domains, diverse geometries, and scenarios with or without external force fields, accommodating Markovian and semi-Markovian random walks. In large systems, first passage time statistics exhibit a bi-scaling behavior, challenging the use of a single time scale. Our theory employs two distinct scaling functions: one for short times, capturing initial dynamics in unbounded systems, and the other for long times is sensitive to finite size effects. The combined framework provides a complete expression for first passage time statistics across all time scales.

Intercalation is a robust method for tuning the physical properties of a vast number of van der Waals (vdW) materials. However, the prospects of using intercalation to modify magnetism in vdWs systems and the associated mechanisms have not been investigated adequately. In this work, we modulate magnetic order in an XY antiferromagnet NiPS3 single crystals by introducing pyridine molecules into the vdWs gap under different thermal conditions. X-ray diffraction measurements indicated pronounced changes in the lattice parameter beta, while magnetization measurements at in-plane and out-of-plane configurations exposed reversal trends in the crystals Neel temperatures through intercalation-de-intercalation processes. The changes in magnetic ordering were also supported by three-dimensional thermal diffusivity experiments. The preferred orientation of the pyridine dipoles within vdW gaps was deciphered via polarized Raman spectroscopy. The results highlight the relation between the preferential alignment of the intercalants, thermal transport, and crystallographic disorder along with the modulation of anisotropy in the magnetic order. The theoretical concept of double-exchange interaction in NiPS3 was employed to explain the intercalation-induced magnetic ordering. The study uncovers the merit of intercalation as a foundation for spin switches and spin transistors in advanced quantum devices.

Classical and wave properties of pseudosphere-shape microlasers are investigated through experiments and numerical simulations. These pseudosphere microlasers are surface-like organic microlasers with constant negative curvature, which were fabricated with high optical quality by direct laser writing. It is shown that they behave, in many ways, similar to two-dimensional flat disks, regardless of the different Gaussian curvature of the two systems. Indeed, it is evidenced that, due to rotational symmetry, the pseudosphere is an integrable system with marginally stable dynamics.

In this work, we elucidate the crucial role of borate anions ([B(OH)4]-) for the electrocatalytic urea oxidation reaction (UOR) using a nanoporous metallic nickel (NP-Ni) catalyst grown on Si substrates. The UOR activity of the NP-Ni catalyst has been studied at various boric acid (H3BO3) concentrations, demonstrating superior activity at a specific electrolytic composition of 0.5 M KOH, 0.33 M urea, and 50 mM of H3BO3. Based on a wide range of electrochemical techniques, such as, cyclic voltammetry (CV), linear sweep voltammetry (LSV), Pb-anodic deposition, and chronoamperometry (CA), we develop a potential mechanism for the [B(OH)4]--mediated UOR. The high double layer capacitance, surface density of Ni redox sites, and urea oxidation currents, clearly demonstrate the significant impact of [B(OH)4]- during electrolysis. Furthermore, we find that UOR catalyzed by the NP-Ni is controlled by diffusion both in presence and absence of [B(OH)4]-. Finally, a set of physical characterizations, including XPS, SEM, and TEM were performed to correlate the composition and structure of the NP-Ni to the [B(OH)4]--mediated increased UOR activity. The boosted UOR we obtain can open new avenues for treatment of wastewater and assist with environmental remediation.

Temporal optics rises from the equivalence between light diffraction in free space and pulse dispersion in dispersive media, paving the way for the development of temporal devices and applications, such as time-lenses. A Four-wave mixing based time-lens allows single-shot measurements of ultra-short signals in high temporal resolution by imaging signals, and inducing temporal Fourier transform. We introduce a cascade time-lens by utilizing a cascade FWM process within the time-lens. We theoretically develop and experimentally demonstrate the cascade time-lens, and confirm that different cascade orders correspond to different effective temporal systems, leading to measuring in various temporal imaging configurations simultaneously with a single optical setup. This approach can simplify experiments and provide a more comprehensive view of a signal’s phase and temporal structure. Such capabilities are …

Rechargeable Zn-air batteries with near-neutral electrolytes hold promise as cheap, safe and sustainable devices, but they suffer from slow charge kinetics and remain poorly studied. Here we reveal a charge storage mechanism of near-neutral Zn-air batteries that is mediated by H2O2 formation upon cell discharge and its oxidation upon charge. The manifestation of this mechanism strongly depends on the electrolyte composition and positive electrode material, being pronounced when ZnSO4 solutions and carbon nanotubes are employed. Oxidation of dissolved H2O2 is facile, enabling oxygen evolution reaction (OER) at low potentials (~1.5 V vs. Zn2+/Zn) which, in contrast to conventional four-electron OER, does not induce corrosion of carbon electrodes. Facilitation of the H2O2-mediated pathway might therefore be helpful for developing high-performance near-neutral Zn-air batteries.

Proteins are attractive as functional components in molecular junctions. However, control-ling the electronic charge transport via proteins, held between two electrodes, requires in-formation on their frontier orbital energy level alignment relative to the electrodes’ Fermi level (EF), which normally requires studies of UV Photoemission Spectroscopy (UPS) with HeI excitation. Such excitation is problematic for proteins, which can denature under stand-ard measuring conditions. Here we use high-sensitivity soft UV photoemission spectroscopy (HS-UPS) combined with Constant Final State Yield Spectroscopy (CFS-YS) to get this in-formation for electrode/protein contacts. Monolayers of the redox protein Azurin, (Az) and its Apo-form on Au substrates, have HOMO onset energies, obtained from CFS-YS, differ by ~ 0.2 eV, showing crucial role of the Cu redox centre in the electron transport process. We find that combined HS-UPS / CFS-YS measurements agree with the Photoelectron Yield Spectroscopy (PYS), showing potential of the HS-UPS + CFS-YS as a powerful tool to char-acterize and map the energetics of a protein-electrode interfaces, which will aid optimizing design of devices with targeted electronic properties, as well as for novel applications.

We investigate a system of Brownian particles weakly bound by attractive parity-symmetric potentials that grow at large distances as , with . The probability density function at long times reaches the Boltzmann-Gibbs equilibrium state, with all moments finite. However, the system's relaxation is not exponential, as is usual for a confining system with a well-defined equilibrium, but instead follows a stretched exponential with exponent . This problem is studied from three perspectives. First, we propose a straightforward and general scaling rate-function solution for . This rate-function, which is an important tool from large deviation theory, also displays anomalous time scaling and a dynamical phase transition. Second, through the eigenfunctions of the Fokker-Planck operator, we obtain, using the WKB method, more complete solutions that reproduce the rate function approach. Finally, we show how the alternative path-integral formalism allows us to recover the same results, with the above rate-function being the solution of the classical Hamilton-Jacobi equation describing the most probable path. Properties such as parity, the role of initial conditions, and the dynamical phase transition are thoroughly studied in all three approaches.

The intrinsic sluggishness of oxygen reduction reaction (ORR) limits the widespread adoption of low-temperature anion exchange membrane fuel cells (AEMFCs) technology, and effective ORR electrocatalysts and methods for ORR enhancement are needed. Herein, we investigate the mechanism behind the improvement of ORR activity of Ag electrocatalyst coated with a shell based on polydopamine (PDA) crosslinked with polyethylene imine (PEI) during AEMFC operation. We show a correlation between electrochemical and physical properties of the PDA/PEI Ag catalyst, with its performance within membrane-electrode assembly (MEA) in practical fuel cell operating environments. Higher current density observed in a catalytic region of polarization curve in AEMFC, matches the positive shift in the half-wave potential of ORR on Ag PDA/PEI as measured by rotating disc electrode (RDE) experiments. Additionally …

Humans develop immunoglobulin G (IgG) antibodies to the foods they consume. In the context of food allergy, allergen-specific IgG antibodies can sequentially class-switch to pathogenic IgE. However, the mechanism underlying the antigenicity of food proteins remains uncharacterized. Here, we identified convergent antibodies arising from different antibody gene rearrangements that bind to the immunodominant peanut allergen Ara h 2 and characterized allelic and junctional constraints on germline antibody specificity. Structurally, we found similar epitope-paratope interactions across multiple gene rearrangements. We demonstrate that these germline-encoded epitope-specific convergent antibodies to peanut occur commonly in the population because of the worldwide prevalence of the relevant gene rearrangements, allelic independence, and junctional malleability. As a result, serum IgG to this public epitope …

Significance Integrating multiple biosensors improves the sensitivity and precision of physiological measurements in healthcare monitoring. By combining sensors that target different physiological parameters, a more comprehensive assessment of a subject’s health can be achieved. Aim We evaluate the performance of two biosensors for extracting cardiac parameters: a textile-based strain sensor for measuring respiratory rate and an optical sensor for measuring heart rate, , and respiratory rate. The objective is to determine optimal placement conditions for each sensor and assess their feasibility for integration into a single wearable system. Approach Two experimental setups were tested. In the first, the strain sensor was placed on the subject’s shirt, while the optical sensor was positioned on the external wrist. In the second, both sensors were placed on the chest, under the shirt. The accuracy and performance …

The recurrence time is the time a process first returns to its initial state. Using quantum walks on a graph, the recurrence time is defined through the stroboscopic monitoring of the arrival of the particle to a node of the system. When the time interval between repeated measurements is tuned in such a way that the eigenvalues of the unitary become degenerate, the mean recurrence time exhibits resonances. These resonances imply faster mean recurrence times, which were recorded on quantum computers. The resonance broadening is captured by a restart uncertainty relation [Yin et al., Proc. Natl. Acad. Sci. USA 122, e2402912121 (2025)]. To ensure a comprehensive analysis, we extend our investigation to include the impact of system size on the widened resonances, showing how the connectivity and energy spectrum structure of a system influence the restart uncertainty relation. Breaking the symmetry of the …

Background/Objectives: To evaluate the concentrations of trace elements in tear fluid among athletes using particle-induced X-ray emission (PIXE), and to assess the associations with gender, sports intensity, and nutritional supplement intake. Methods: In this cohort study, 84 athletes engaged in high- or low-intensity sports completed a demographic and supplement-use questionnaire. Tear samples were collected using Schirmer strips and analyzed for elemental composition with PIXE, a high-sensitivity technique suited for small biological samples. Multivariate and nonparametric statistical analyses were used to compare groups. Results: There were 46 males and 38 females, aged 17–63 years (mean 30.21 years). Tear phosphorus, potassium, and sulfur concentrations were higher in women than men and higher in women participating in low-intensity compared to high-intensity sports. Tear concentrations of magnesium were higher in men participating in high-intensity sports compared to low-intensity sports. They were higher in men than women regardless of supplement intake. Iron concentrations were higher in men than women only when neither group was taking supplements. Smoking had a slight inverse relationship to iron values. Iron levels were particularly high in men participating in intense sports and low in smokers. Magnesium supplements were associated with raised magnesium levels in tears. Conclusions: This study demonstrates an association between trace element levels in human tears and gender, sports intensity, and food supplement intake. PIXE enables the evaluation of trace element concentration in tears, which may …

Adenosine deaminases acting on RNA (ADAR) enzymes constitute a natural cellular mechanism that induces A-to-I(G) editing, introducing genetic changes at the RNA level. Recently, interest in the endogenous-ADAR editor has emerged for correcting genetic mutations, consisting of a programmed oligonucleotide that attracts the native ADAR, thereby offering opportunities for medical therapy. Here, we systematically chart the scope of cancer mutations that endogenous-ADAR can correct. First, analyzing germline single nucleotide variants in cancer predisposition genes, we find that endogenous-ADAR can revert a fifth of them, reducing the risk of cancer development later in life. Second, examining somatic mutations across various cancer types, we find that it has the potential to correct at least one driver mutation in over a third of the samples, suggesting a promising future treatment strategy. We also …

Humans develop immunoglobulin G (IgG) antibodies to the foods they consume. In the context of food allergy, allergen-specific IgG antibodies can sequentially class-switch to pathogenic IgE. However, the mechanism underlying the antigenicity of food proteins remains uncharacterized. Here, we identified convergent antibodies arising from different antibody gene rearrangements that bind to the immunodominant peanut allergen Ara h 2 and characterized allelic and junctional constraints on germline antibody specificity. Structurally, we found similar epitope-paratope interactions across multiple gene rearrangements. We demonstrate that these germline-encoded epitope-specific convergent antibodies to peanut occur commonly in the population because of the worldwide prevalence of the relevant gene rearrangements, allelic independence, and junctional malleability. As a result, serum IgG to this public epitope …

A longstanding question in type 1 diabetes (T1D) research pertains to the selective loss of β-cells whilst neighboring islet α-cells remain unharmed. Here we demonstrate differential sensitivity of mouse α- and β-cells to deficient RNA editing, a cellular process that prevents double-stranded RNA (dsRNA)-mediated activation of a type I interferon (IFN) response. Mosaic disruption of the RNA editing enzyme Adar in mouse β-cells triggers a massive interferon response, islet inflammation and mutant β-cell destruction. Surprisingly, wild type β-cells are also eliminated while neighboring α-cells are unaffected. α-cell Adar deletion leads to only a slight elevation in interferon signature and does not elicit inflammation nor a metabolic phenotype. Concomitant deletion of Adar in α- and β-cells leads to elimination of both cell populations, suggesting that in contrast to β-cells, α-cell death requires both cell autonomous …

The controlled manipulation of the secondary structure of guanine quadruplexes (GQs) using ligands has been extensively employed in the field of DNA biotechnology. However, there is little predictability for such processes based on the sequence of the DNA target. Herein, we explored the impact of GQ sequence identity on the kinetics of this chaperone-like binding mechanism and its influence on subsequent sequence preference. We monitored the topological conversion of flexible, non-parallel GQs, encoding for two iso-compositional groups, that is induced by the microperoxidase-11 ligand. We found that within each group of GQs, the activation energy for the binding process is linearly related to the melting temperature of the individual sequences, regardless of their composition or topology. These results shed light on the chaperone-like mechanism and open new avenues for designing ligands with sequence …