BINA

Millions of adenosines are deaminated throughout the transcriptome by ADAR1 and ADAR2, modulating double-stranded RNA (dsRNA) immunogenicity and recoding mRNA. The high variability in the susceptibility of different adenosines to editing begs the question of what are the determinants of substrate specificity. Here, we systematically monitor how secondary structure modulates ADAR2 vs ADAR1 substrate selectivity, on the basis of systematic probing of thousands of synthetic sequences transfected into ADAR1-deleted cell lines exogenously expressing either ADAR2 or ADAR1. In both cases, structural disruptions gave rise to symmetric, strand-specific induced editing at a fixed offset, but of varying length: -26 nt for ADAR2, and -35 nt for ADAR1. We dissect the basis for the differences in offset between ADAR1 and ADAR2 via diverse mutants, domain-swaps, and ADAR evolutionary homologs, and reveal that it is encoded by the differential RNA binding domain architecture. We demonstrate that this offset-enhanced editing can allow an improved design of ADAR2-recruiting therapeutics, with proof-of-concept experiments suggestive of increased on-target and potentially decreased off-target editing. Our findings provide novel insight into the determinants guiding ADAR2 substrate selectivity and into the roles of the RNA binding domains of ADAR1 and ADAR2 in mediating differential targeting, and should facilitate the design of improved ADAR-recruiting therapeutics.

Analysis of an individual's immunoglobulin (IG) gene repertoire requires the use of high-quality germline gene Reference Sets. The Adaptive Immune Receptor Repertoire-Community (AIRR-C) Reference Sets have been developed to include only human IG heavy and light chain alleles that have been confirmed by evidence from multiple high-quality sources. By including only those alleles with a high level of support, including some new sequences that currently lack official names, AIRR-seq analysis will have greater accuracy and studies of the evolution of immunoglobulin genes, their allelic variants and the expressed immune repertoire will be facilitated. Although containing less than half the previously recognised IG alleles (e.g. just 198 IGHV sequences), the Reference Sets eliminated erroneous calls and provided excellent coverage when tested on a set of repertoires from 99 individuals comprising over 4 million V(D)J rearrangements. To improve AIRR-seq analysis, some alleles have been extended to deal with short 3' or 5' truncations that can lead them to be overlooked by alignment utilities. To avoid other challenges for analysis programs, exact paralogs (e.g. IGHV1-69*01 and IGHV1-69D*01) are only represented once in each set, though alternative sequence names are noted in accompanying metadata. The Reference Sets also include novel alleles: 8 IGHV alleles, 2 IGKV alleles and 5 IGLV alleles. The version-tracked AIRR-C Reference Sets are freely available at the OGRDB website (https://ogrdb.airr-community.org/germline_sets/Human) and will be regularly updated to include newly-observed and previously-reported …

Morphogenesis involves the transformation of initially simple shapes, such as multicellular spheroids, into more complex 3D shapes. These shape changes are governed by mechanical forces including molecular motor-generated forces as well as hydrostatic fluid pressure, both of which are actively regulated in living matter through mechano-chemical feedback. Inspired by autonomous, biophysical shape change, such as occurring in the model organism hydra, we introduce a minimal, active, elastic model featuring a network of springs in a globe-like spherical shell geometry. In this model there is coupling between activity and the shape of the shell: if the local curvature of a filament represented by a spring falls below a critical value, its elastic constant is actively changed. This results in deformation of the springs that changes the shape of the shell. By combining excitation of springs and pressure regulation, we …

Lithiated oxides like Li[NixCoyMnz]O2 (x + y + z = 1) with high nickel content (x ≥ 0.8) can possess high specific capacity ≥200 mA h g−1 and have attracted extensive attention as perspective cathode materials for advanced lithium-ion batteries. In this work, we synthesized LiNi0.9Co0.1O2 (NC90) materials and studied their structural characteristics, electrochemical performance, and thermal behavior in Li-cells. We developed modified cationic-doped NC90 samples with greatly improved properties due to doping with Mo6+ and B3+ and dual doping via simultaneous modification with these dopants. The main results of the current study are significantly higher capacity retention, greatly reduced voltage hysteresis, and considerably decreased charge-transfer resistance of the Mo and Mo–B doped electrodes compared to the undoped ones upon prolonged cycling. We also revealed remarkable microstructural …

Second harmonic generation (SHG) is forbidden for centrosymmetric materials such metals. Yet, symmetry can be broken by introducing plasmonic nano-structures which lead to enhancement of the electromagnetic field at both the fundamental and the SH frequencies. Using non-linear microscopy, we experimentally demonstrate enhanced SHG from isosceles triangular cavities (~215 nm side length, 200 nm base) milled in thin aluminum film. Upon strong interaction between the cavities, they behave as a single unit and response in a coherent manner, i.e. SHG is observed from the coupled system. The hybridization between the cavities is not only dependent on the distance between them, but their spatial arrangement is found to be a crucial parameter. That is, the SHG efficiency can be enhanced upon different arrangement of the same cavities, holding the same distance between them. We characterize those …

T-cell diversity is crucial for producing effective receptors that can recognize the pathogens encountered throughout life. A stochastic biological process known as VDJ recombination accounts for the high diversity of these receptors, making their analysis challenging. We present a new approach to sequence encoding and analysis, based on the Lempel-Ziv 76 algorithm (LZ-76). By creating a graph-like model, we identify specific sequence features and produce a new encoding approach to an individual's repertoire. We demonstrate that this repertoire representation allows for various applications, such as generation probability inference, informative feature vector derivation, sequence generation, and a new measure for diversity estimation.

Chaos, namely exponential sensitivity to initial conditions, is generally considered a nuisance, inasmuch as it prevents long‐term predictions in physical systems. Here, an easily accessible approach to undo deterministic chaos and tailor ray trajectories in arbitrary 2D optical billiards by introducing spatially varying refractive index therein is presented. A new refractive index landscape is obtained by a conformal mapping, which makes the trajectories of the chaotic billiard fully predictable and the billiard fully integrable. Moreover, trajectory rectification can be pushed a step further by relating chaotic billiards with non‐Euclidean geometries. Two examples are illustrated by projecting billiards built on a sphere as well as the deformed spacetime outside a Schwarzschild black hole, which respectively lead to all periodic orbits and spiraling trajectories remaining away from the boundaries of the transformed 2D billiards …

Micro- and Nano-particles are elemental for many current and developing technologies. Specifically, these particles are being extensively used in biological studies and applications, including imaging, drug delivery and therapeutics. Recent advances have led to the development of multifunctional particles, which have the potential to further enhance their effectiveness, enabling novel applications. Therefore, many efforts are devoted to produce well-defined particles for specific needs. However, conventional fabrication methodologies utilized to develop particles are time consuming, making it extremely challenging to fine-tune properties of the particles for multifunctional applications. Herein, we present a simple and facile method to fabricate dome-shaped micron and nano particles by a robust physical route. The presented method enables to design particles with a vast range of materials, sizes and compositions …

Emerging energy storage systems based on abundant and cost-effective materials are key to overcome the global energy and climate crisis of the 21st century. Rechargeable Magnesium Batteries (RMB), based on Earth-abundant magnesium, can provide a cheap and environmentally responsible alternative to the benchmark Li-ion technology, especially for large energy storage applications. Currently, RMB technology is the subject of intense research efforts at laboratory scale. However, these emerging approaches must be placed in a real-world perspective to ensure that they satisfy key technological requirements. In an attempt to bridge the gap between laboratory advancements and industrial development demands, herein, we report the first non-aqueous multilayer RMB pouch cell prototypes and propose a roadmap for a new advanced RMB chemistry. Through this work, we aim to show the great unrealized …

Ultrasonic irradiation of molten metals in liquid media causes dispersion of the metals into suspensions of micro- and nanoparticles that can be separated. This is applicable mainly to low-mp elemental metals or alloys, but higher mp elemental metals or alloys were also reported. Among metals, mercury and gallium exhibit especially-low melting points and are thus considered as liquid metals (LMs). Sonication of mercury in aqueous solutions of certain metal ions can cause simultaneous reduction of the ions and reactions between the metals. Gallium can be melted and sonicated in warm water, as well as in aqueous solutions of various solutes such as metal ions and organic compounds, which opened a wide window of interactions between the gallium particles and the solutes. Sonication of molten metals in organic liquids, such as polyethylene glycol (PEG) 400, forms carbon dots (C-dots) doped with …

Cancer remains a leading cause of death globally (1). The conventional methods of treatment offered are radiation (2), chemotherapy (3), immunotherapy (4), surgery, and recently nanotechnology (nanomedicine and nano-processes)(5). Every cancer treatment can be defined and evaluated based on its efficiency, selectivity, side effects, and economic cost (6). However, combining predictive models and advanced machine learning methods with these cancer therapies may enhance their overall efficiency and selectivity, as well as the safety of the patient.Radiation Therapy (RT), also known as radiotherapy, is a non-surgical intervention frequently used in cancer treatment (2). This method is based on a high-level focused dose of radiation directed toward the tumor. This deposit of highenergy radiation kills cancer cells or decelerates their growth by damaging their DNA (2). Nevertheless, the challenges of RT include damage to tumor-proximate normal cells, the inability to radiate minor tumors out of scope of the imaging scans, patient movement, and low oxygen supply (7, 8). Therefore, many researchers are working on the development of targeted radiation methods to deliver a higher dose of radiation to the tumor with improved selectivity. Recently, the combination of nanotechnology with laser radiation has been demonstrated to represent a safe set of modalities for tumor destruction with high specificity (9). In particular, this involves the use of light-controlled nanoparticles (NPs) that can be activated via a light of a specific wavelength to form highly efficient and selective systems in the nanometer range (10). These NPs accumulate specifically …

Cancer remains a leading cause of death globally (1). The conventional methods of treatment offered are radiation (2), chemotherapy (3), immunotherapy (4), surgery, and recently nanotechnology (nanomedicine and nano-processes)(5). Every cancer treatment can be defined and evaluated based on its efficiency, selectivity, side effects, and economic cost (6). However, combining predictive models and advanced machine learning methods with these cancer therapies may enhance their overall efficiency and selectivity, as well as the safety of the patient.Radiation Therapy (RT), also known as radiotherapy, is a non-surgical intervention frequently used in cancer treatment (2). This method is based on a high-level focused dose of radiation directed toward the tumor. This deposit of highenergy radiation kills cancer cells or decelerates their growth by damaging their DNA (2). Nevertheless, the challenges of RT include damage to tumor-proximate normal cells, the inability to radiate minor tumors out of scope of the imaging scans, patient movement, and low oxygen supply (7, 8). Therefore, many researchers are working on the development of targeted radiation methods to deliver a higher dose of radiation to the tumor with improved selectivity. Recently, the combination of nanotechnology with laser radiation has been demonstrated to represent a safe set of modalities for tumor destruction with high specificity (9). In particular, this involves the use of light-controlled nanoparticles (NPs) that can be activated via a light of a specific wavelength to form highly efficient and selective systems in the nanometer range (10). These NPs accumulate specifically …

Total internal reflection fluorescence (TIRF) has come of age, but a reliable and easy-to-use tool for calibrating evanescent-wave penetration depths is missing. We provide a test-sample for TIRF and other axial super-resolution microscopies for emitter axial calibration. Our originality is that nanometer(nm) distances along the microscope’s optical axis are color-encoded in the form of a multi-layered multi-colored transparent sandwich. Emitter layers are excited by the same laser but they emit in different colors. Layers are deposited in a controlled manner onto a glass substrate and protected with a non-fluorescent polymer. Decoding the penetration depth of the exciting evanescent field, by spectrally unmixing of multi-colored samples is presented as well. Our slide can serve as a test sample for quantifying TIRF, but also as an axial ruler for nm-axial distance measurements in single-molecule localization …

One of the problems associated with conducting a membrane filtration process is the accumulation of undesirable material on the surface of membranes. The deposited layer can significantly increase the resistance of the membrane, which leads to a reduction of the process efficacy. In many cases, the service life of the membranes is also reduced. One type of contamination that can accumulate on the surface of membranes are biological species (i.e., microorganisms). The process is called biofouling and can lead to a biofilm formation, which constitutes an integral layer resistant or completely invulnerable to many commonly used cleaning techniques. Various microorganisms, including bacteria, fungi and algae, proliferate and colonize the available surface of the membranes. Adhesion to the surface is enabled by secreted components known as extracellular polymeric substances, thanks to which a biofilm is formed on the surface. In order to reduce the intensity of biofouling, the membranes are subjected to various modification techniques. One of the modification techniques is the addition of particles with antimicrobial and anti-biofouling properties to the polymer at the stage of membrane production. In this study, copper oxide (CuO) was used as an antimicrobial material, which was added, as a nanopowder, to a polysulfone solution. From the prepared membrane-forming solution, flat ultrafiltration membranes were produced using the wet phase inversion method. The secondary solvent was the ultrapure water. The aim of the conducted research was to produce membranes with anti-biofouling properties and to characterize them in terms of …

Confocal microscopes have been the workhorses of 3-D biological imaging, but they are slow, offer limited depth penetration and collect only ballistic photons. With their inefficient use of excitation photons they expose biological samples to an often intolerably high light burden. The speed limitation and photo-bleaching risk can be somewhat relaxed in a spinning-disk geometry, due to shorter pixel dwell times and rapid re-scans during image capture. Alternatively, light-sheet microscopes rapidly image large volumes of transparent or chemically cleared samples. Finally, with infrared excitation and efficient scattered-light collection, 2-photon microscopy allows deep-tissue imaging, but it remains slow. Here, we describe a new optical scheme that borrows the best from three different worlds: the speed and direct-view from a spinning-disk confocal, deep tissue-penetration and intrinsic optical sectioning from 2-photon …

Climate change calls for a change in the way we use and produce energy, and carbon-free has become the future direction of energy production and utilization. To obtain this, we must rely on sustainable energy sources such as wind and sun, but their intermittence limits the production of clean energy to only a few hours a day. To overcome this issue, energy storage and production technologies must be developed. Although several technologies have been proposed, the only viable scheme that could allow short-to-long-term storage and efficient energy transportation at-scale is the hydrogen economy, which relies on three pillars of technology: electrolyzers, hydrogen storage and fuel cells. In recent years, there have been rapid technological advances in hydrogen production, new hydrogen storage materials, and high-performance hydrogen fuel cells, etc. However, there are still numerous technological difficulties …

Platinum group metal‐free catalysts have been considered the most promising alternative for platinum‐based catalysts for the oxygen reduction reaction in fuel cells. Despite the significant advancement made in activity, their viability as fuel cell catalysts is still questionable due to their low durability. So far, deciphering the degradation mechanisms of this class of catalysts has been hampered by their undefined structure. Herein, we used a molecular model catalyst, iron‐phthalocyanine, featuring Fe−N4 active sites with resemblance to those in the more active Fe−N−C catalysts, and studied their degradation mechanisms. Based on X‐ray photoelectron spectroscopy and the electrochemical measurements, three main demetallation processes were identified: at potentials higher than 0.65 V vs. RHE, where the metal center is Fe3+, an electrochemical oxidation of the ligand ring is occurring, between 0.6 and 0.2 V …

The characterization of ultrathin transparent films is paramount for various optoelectronic materials, coatings, and photonics. However, characterizing such thin layers is difficult and it requires specialized clean‐room equipment and trained personnel. Here, a contact‐less, all‐optical method is introduced and validated for characterizing nanometric transparent films using far‐field optics. A series of nanometric, smooth, and homogeneous layered samples are fabricated first, alternating transparent spacer and fluorescent layers in a controlled manner. Fluorescence radiation pattern originating from the thin fluorophore layers is then recorded and analyzed and quantitative image analysis is used to perform in operando measurements of the refractive index, film homogeneity and to estimate axial fluorophore distances at a sub‐wavelength scale with a precision of a few of nanometers. The results compare favorably to …

Dynamics and Fluctuations in Biomedical Photonics XX Page 1 PROGRESS IN BIOMEDICAL OPTICS AND IMAGING Vol. 24 No. 27 Volume 12378 Proceedings of SPIE, 1605-7422, V. 12378 SPIE is an international society advancing an interdisciplinary approach to the science and application of light. Dynamics and Fluctuations in Biomedical Photonics XX Valery V. Tuchin Martin J. Leahy Ruikang K. Wang Zeev Zalevsky Editors 29–30 January 2023 San Francisco, California, United States Sponsored and Published by SPIE Dynamics and Fluctuations in Biomedical Photonics XX, edited by Valery V. Tuchin, Martin J. Leahy, Ruikang K. Wang, Zeev Zalevsky, Proc. of SPIE Vol. 12378, 1237801 · © 2023 SPIE · 1605-7422 · doi: 10.1117/12.2676834 Proc. of SPIE Vol. 12378 1237801-1 Page 2 The papers in this volume were part of the technical conference cited on the cover and title page. Papers were selected and …

TiO2 material has gained significant attention for large‐scale energy storage due to its abundant, low‐cost, and environmentally friendly properties, as well as the availability of various nanostructures. Phosphorus doping has been established as an effective technique for improving electronic conductivity and managing the slow ionic diffusion kinetics of TiO2. In this study, non‐doped and phosphorus doped TiO2 materials were synthesized using sodium alginate biopolymer as chelating agent. The prepared materials were evaluated as anode materials for Lithium‐Ion Batteries (LIBs). The electrodes exhibit remarkable electrochemical performance, including a high reversible capacity of 235 mAh g‐1 at 0.1C and excellent first coulombic efficiency of 99%. An integrated approach, combining Operando XRD and Ex‐situ XAS, comprehensively investigates the relationship between phosphorus doping, material …

TiO2 material has gained significant attention for large‐scale energy storage due to its abundant, low‐cost, and environmentally friendly properties, as well as the availability of various nanostructures. Phosphorus doping has been established as an effective technique for improving electronic conductivity and managing the slow ionic diffusion kinetics of TiO2. In this study, non‐doped and phosphorus doped TiO2 materials were synthesized using sodium alginate biopolymer as chelating agent. The prepared materials were evaluated as anode materials for lithium‐ion batteries (LIBs). The electrodes exhibit remarkable electrochemical performance, including a high reversible capacity of 235 mAh g−1 at 0.1 C and excellent first coulombic efficiency of 99 %. An integrated approach, combining operando XRD and ex‐situ XAS, comprehensively investigates the relationship between phosphorus doping, material …