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Apr 2021 • Molecular cell

Deciphering the principles of the RNA editing code via large-scale systematic probing

Anna Uzonyi, Ronit Nir, Ofir Shliefer, Noam Stern-Ginossar, Yaron Antebi, Yonatan Stelzer, Erez Y Levanon, Schraga Schwartz

Adenosine-to-inosine editing is catalyzed by ADAR1 at thousands of sites transcriptome-wide. Despite intense interest in ADAR1 from physiological, bioengineering, and therapeutic perspectives, the rules of ADAR1 substrate selection are poorly understood. Here, we used large-scale systematic probing of ∼2,000 synthetic constructs to explore the structure and sequence context determining editability. We uncover two structural layers determining the formation and propagation of A-to-I editing, independent of sequence. First, editing is robustly induced at fixed intervals of 35 bp upstream and 30 bp downstream of structural disruptions. Second, editing is symmetrically introduced on opposite sites on a double-stranded structure. Our findings suggest a recursive model for RNA editing, whereby the structural alteration induced by the editing at one site iteratively gives rise to the formation of an additional editing site …

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Apr 2021

Supplementary Info: Multi-parameter photon-by-photon hidden Markov modeling

Paul David Harris, Shimon Weiss, Eitan Lerner, Edmond J Safra Campus

All code and raw data (in the form of photon-HDF5 files) is available for download here:(https://zenodo. org/record/4671393 [1]). Data must be extracted from the FRETbursts [2] data structure, and cast such that the H2MM_C package [3] can process it. In the H2MM algorithm, photons are identified by an unsigned integer index, and an unsigned integer arrival time. A burst consists of two arrays of equal length, one for the indexes, and the other for the arrival times (in the form of one dimensional numpy arrays). The python function accepts as input an initiating H2MM state model (implemented as a python extension type in the H2MM_C package [3]), a python list of the arrays of the photon indexes, and a separate python list of the arrays of the photon arrival times. FRETbursts identifies streams according to the following convention: the excitation period∗ harripd@ gmail. com† eitan. lerner@ mail. huji. ac. il

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Apr 2021 • arXiv preprint arXiv:2104.03816

Transitions in the ergodicity of subrecoil-laser-cooled gases

Eli Barkai, Günter Radons, Takuma Akimoto

With subrecoil-laser-cooled atoms one may reach nano-Kelvin temperatures while the ergodic properties of these systems do not follow usual statistical laws. Instead, due to an ingenious trapping mechanism in momentum space, power-law-distributed sojourn times are found for the cooled particles. Here, we show how this gives rise to a statistical-mechanical framework based on infinite ergodic theory, which replaces ordinary ergodic statistical physics of a thermal gas of atoms. In particular, the energy of the system exhibits a sharp discontinuous transition in its ergodic properties. Physically this is controlled by the fluorescence rate, but more profoundly it is a manifestation of a transition for any observable, from being an integrable to becoming a non-integrable observable, with respect to the infinite (non-normalised) invariant density.

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Apr 2021 • Polymers for Advanced Technologies

Layer by layer controlled synthesis at room temperature of tri‐modal (MRI, fluorescence and CT) core/shell superparamagnetic IO/human serum albumin nanoparticles for diagnostic …

Sayan Ganguly, Igor Grinberg, Shlomo Margel

Magnetic nanoparticles (NPs) are drawing attention since few decades because of its tunable properties. It is well known that the degradation of plasma proteins like albumin in cancer cells is significantly faster than in normal cells. Hereby, we combined the advantages of human serum albumin (HSA) and iron oxide NPs (IO NPs) to prepare mono‐, bi‐ and tri‐modal IO/HSA core‐shell NPs for diagnostic applications, to promote the smooth and precise assessment of signals obtained from diagnostic machines. HSA is well known as a physiological carrier for many biomaterials (e.g., fatty acids, metal ions, amino acids, peptides, drugs, etc.). Mono‐modal magnetic resonance imaging (MRI) IO NPs were prepared via nucleation at room temperature of IO layers onto IO‐HSA nuclei. Mono‐modal IO/HSA NPs were produced by heating the IO NPs aqueous HSA dispersion to 80°C, followed by HSA precipitation via …

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Apr 2021 • Nature Photonics

A wavelength-scale black phosphorus spectrometer

Shaofan Yuan, Doron Naveh, Kenji Watanabe, Takashi Taniguchi, Fengnian Xia

On-chip spectrometers with compact footprints are being extensively investigated owing to their promising future in critical applications such as sensing, surveillance and spectral imaging. Most existing miniaturized spectrometers use large arrays of photodetection elements to capture different spectral components of incident light, from which its spectrum is reconstructed. Here, we demonstrate a mid-infrared spectrometer in the 2–9 µm spectral range, utilizing a single tunable black phosphorus photodetector with an active area footprint of only 9× 16 µm 2, along with a unique spectral learning procedure. Such a single-detector spectrometer has a compact size at the scale of the operational wavelength. Leveraging the wavelength and bias-dependent responsivity matrix learned from the spectra of a tunable blackbody source, we reconstruct unknown spectra from their corresponding photoresponse vectors. Enabled …

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Apr 2021 • Nano-Structures & Nano-Objects

Biocompatible N-doped carbon dots for the eradication of methicillin-resistant S. aureus (MRSA) and sensitive analysis for europium (III)

Moorthy Maruthapandi, Poushali Das, Arumugam Saravanan, Michal Natan, Ehud Banin, Sriram Kannan, Shulamit Michaeli, John HT Luong, Aharon Gedanken

Plant leaves have more attracted in the preparation of carbon dots (CDs) owing to natural phytochemicals. Herein, we performed a one-pot hydrothermal process for the synthesis of Nitrogen doped CDs (N@ CDs) from glossy heart-shaped Piper betel leaves (P. betel). The prepared N@ CDs were effectively applied for the eradication of E. coli, S. aureus, and methicillin-resistant S. aureus (MRSA). The N@ CDs were also used as a sensor for lanthanides detection with notable selectivity for Eu 3+. The results revealed that the water-soluble N@ CDs displayed narrow size particle distribution with a mean diameter of 2.6 nm. The bright fluorescence was estimated to be at λ ex: 350 with λ em: 430 nm. The functional groups on N@ CDs were confirmed by FTIR and XPS. The antimicrobial effect of N@ CDs was concentration-dependent and effectively against E. coli and S. aureus at 1000 μ g/mL. The antibacterial …

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Apr 2021 • Journal of Laser Micro/Nanoengineering

Influence of Nanosecond Pulse Bursts at High Repetition Rates on Ablation Process

John Linden, Sharona Cohen, Yuval Berg, Zvi Kotler, Zeev Zalevsky

Nanosecond laser pulsed ablation is a common technique for micromachining of microelectronics. Recent laser technologies use temporal shaping of single pulses to create ‘pulse bursts’ of several short consecutive pulses at several times the laser repetition rate with a reduced peak power, achieving significantly higher average powers. In this study we tested the effects of pulse bursts on ablation of multilayer PCB. We show that by implementing temporal beam shaping, we were able to increase the throughput by a factor of 40%. To gain a deeper insight of the laser mater interactions of ablation with pulse bursts, we studied the plasma emissions and monitor the process with a time resolution of several nanoseconds. These results demonstrate the importance of temporal pulse shapes for laser micromachining in the microelectronics industry.

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Apr 2021 • ChemSusChem

Optimization of Ni− Co− Fe‐Based Catalysts for Oxygen Evolution Reaction by Surface and Relaxation Phenomena Analysis

Rinat Attias, Kalimuthu Vijaya Sankar, Kapil Dhaka, Wenjamin Moschkowitsch, Lior Elbaz, Maytal Caspary Toroker, Yoed Tsur

Trimetallic double hydroxide NiFeCoÀ OH is prepared by coprecipitation, from which three different catalysts are fabricated by different heat treatments, all at 350 C maximum temperature. Among the prepared catalysts, the one prepared at a heating and cooling rate of 2 C minÀ 1 in N2 atmosphere (designated NiFeCoÀ N2-2 C) displays the best catalytic properties after stability testing, exhibiting a high current density (9.06 mA cmÀ 2 at 320 mV), low Tafel slope (72.9 mVdecÀ 1), good stability (over 20 h), high turnover frequency (0.304 sÀ 1), and high mass activity (46.52 AgÀ 1 at 320 mV). Stability tests reveal that the hydroxide phase is less suitable for long-term use than catalysts with an oxide phase. Two causes are identified for the loss of stability in the hydroxide phase: a) Modeling of the distribution function of relaxation times (DFRT) reveals the increase in resistance contributed by various relaxation processes; b) density functional theory (DFT) surface energy calculations reveal that the higher surface energy of the hydroxide-phase catalyst impairs the stability. These findings represent a new strategy to optimize catalysts for water splitting.

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Apr 2021 • OSA Continuum

Optical analysis of facial nerve degeneration in Bell’s palsy

Hadas Lupa Yitzhak, Michael Wolf, Nisan Ozana, Yarden Tzabari Kelman, Zeev Zalevsky

This paper is an initial proof of concept for an optical speckled-based method for the evaluation of facial nerve paralysis. Differences between the affected and the healthy sides of the face were measured in patients with Bell's palsy—a peripheral facial nerve paralysis. The patients’ faces were illuminated with two symmetrical spots on their nasolabial folds and the reflected speckle patterns were analyzed. Muscle activity was evaluated by muscle tone contraction-release motion inducing associated skin tilting movements. The skin movements were imaged with a defocused lens, which enables extraction of the speckle pattern's time changing trajectory. We found an asymmetry ratio expression that may be the key for the estimation of the degeneration level in Bell's palsy.

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Apr 2021 • OSA Continuum

Ultra-fast remote photoacoustic imaging with a non-scanning speckle-based setup

Matan Benyamin, Hadar Genish, Ran Califa, Nisan Ozana, Benjamin Lengenfelder, Florian Klämpfl, Zeev Zalevsky

A method for fast non-scanning remote photoacoustic imaging is presented and experimentally demonstrated. The approach is based on speckle contrast measurement, proceeding the previously developed method for speckle contrast based photoacoustic detection. This previously developed method is now presented without the need for raster scanning of the sample, an advantage rarely found in optical photoacoustic detection, and offers 50 times faster as well as a simpler remote photoacoustic scheme in respect to interferometric available solutions.

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Apr 2021 • IEEE Photonics Journal

Comment on “Rapid Image Reconstruction of Structured Illumination Microscopy Directly in the Spatial Domain” and More About Point Spread Function Shaping for Enhanced Imaging …

Dror Fixler, Zeev Zalevsky

During the past several decades, a variety of imaging modalities in fluorescence microscopy have emerged as powerful tools for probing the spatial and temporal dimensions in fixed and living cells and tissues to uncover structural and dynamic information. Recently, our journal accepted a paper in this topic, and we received comments. We found it as opportunity to discuss this important topic for additional angles. We believe that this discussion will be interesting and helpful to the whole community.

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Apr 2021 • Immunologic Research

Exploring genetic defects in adults who were clinically diagnosed as severe combined immune deficiency during infancy

Ido Somekh, Atar Lev, Ortal Barel, Yu Nee Lee, Ayal Hendel, Amos J Simon, Raz Somech

Genetic diagnostic tools including whole-exome sequencing (WES) have advanced our understanding in human diseases and become common practice in diagnosing patients with suspected primary immune deficiencies. Establishing a genetic diagnosis is of paramount importance for tailoring adequate therapeutic regimens, including identifying the need for hematopoietic stem cell transplantation (HSCT) and genetic-based therapies. Here, we genetically studied two adult patients who were clinically diagnosed during infancy with severe combined immune deficiency (SCID). Two unrelated patients, both of consanguineous kindred, underwent WES in adulthood, 2 decades after their initial clinical manifestations. Upon clinical presentation, immunological workup was performed, which led to a diagnosis of SCID. The patients presented during infancy with failure to thrive, generalized erythematous rash …

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Apr 2021 • Advanced Functional Materials

Bipyridine modified conjugated carbon aerogels as a platform for the electrocatalysis of oxygen reduction reaction

Leigh Peles‐Strahl, Noam Zion, Oran Lori, Naomi Levy, Galit Bar, Adi Dahan, Lior Elbaz

Aerogels offer a great platform for heterogeneous electrocatalysis owing to their high surface area and porosity. Atomically dispersed transition metal ions can be imbedded in these platforms at ultra‐high site density to make them catalytically active for various reactions. Herein, the synthesis of a new class of conjugated microporous organic aerogels that are used as covalent 3D frameworks for the electrocatalysis of oxygen reduction reaction (ORR) is reported. Modified aerogels functionalized with bipyridine ligands enable copper ion complexation in a single‐step synthesis. The aerogels’ structures are fully characterized using a wide array of spectroscopic and microscopic methods, and heat‐treated in order to make them electronically conductive. After heat treatment at 600 °C, the aerogels maintained their macrostructure and became active ORR catalysts in alkaline environment, showing high mass activity …

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Apr 2021 • Journal of Medical Engineering & Technology

Validation of a novel contact-free heart and respiratory rate monitor

Ofer Havakuk, Ben Sadeh, Ilan Merdler, Zeev Zalevsky, Javier Garcia-Monreal, Sagi Polani, Yaron Arbel

There is a growing need for remote monitoring of patients due to a lack of resources and infection control. Current systems use sensors that require constant physical contact with the user, which may result in discomfort or lack of adherence. In the present study, we evaluated the accuracy of a new contact-free system to monitor heart and respiratory rate. Study participants were measured simultaneously using two devices: a contact-free optical system that measures nano-vibrations and movements (investigational device, “Gili Pro BioSensor”) and a standard reference bed-side monitor, inclusive of an electrocardiogram and capnograph modules (Mindray®). Co-primary endpoints included HR and RR accuracy in subjects without active arrhythmias for HR, and for all study populations for RR (i.e., for subjects with and without active arrhythmias). Confirmatory secondary endpoints included HR scored continuously for …

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Apr 2021 • Biophysical Journal

Sequence effects on internal structure of droplets of associative polymers

Kulveer Singh, Yitzhak Rabin

Intrinsically disordered proteins (IDPs) can form liquid-like membraneless organelles, gels, and fibers in cells and in vitro. In this study, we propose a simple model of IDPs as associative polymers in poor solvent and explore the formation of transient liquid droplets and their transformation into solid-like aggregates. We use Langevin dynamics simulations of short polymers with two stickers placed symmetrically along their contour to study the effect of the primary sequence of these polymers on their organization inside condensed droplets. We observe that the shape, size, and number of sticker clusters inside the droplet change from a long cylindrical fiber to many compact clusters as one varies the location of stickers along the chain contour. Aging caused by the conversion of intramoleclular to intermolecular associations is observed in droplets of telechelic polymers but not for other sequences of associating …

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Apr 2021 • Leukemia

RNA editing contributes to epitranscriptome diversity in chronic lymphocytic leukemia

Franz J Gassner, Nadja Zaborsky, Ilana Buchumenski, Erez Y Levanon, Matthias Gatterbauer, Maria Schubert, Stefanie Rauscher, Daniel Hebenstreit, Ferran Nadeu, Elias Campo, Alexander Egle, Richard Greil, Roland Geisberger

RNA editing—primarily conversion of adenosine to inosine (A> I)—is a widespread posttranscriptional mechanism, mediated by Adenosine Deaminases acting on RNA (ADAR) enzymes to alter the RNA sequence of primary transcripts. Hence, in addition to somatic mutations and alternative RNA splicing, RNA editing can be a further source for recoding events. Although RNA editing has been detected in many solid cancers and normal tissue, RNA editing in chronic lymphocytic leukemia (CLL) has not been addressed so far. We determined global RNA editing and recurrent, recoding RNA editing events from matched RNA-sequencing and whole exome sequencing data in CLL samples from 45 untreated patients. RNA editing was verified in a validation cohort of 98 CLL patients and revealed substantially altered RNA editing profiles in CLL compared with normal B cells. We further found that RNA editing patterns …

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Apr 2021 • arXiv preprint arXiv:2104.06232

Driving quantum systems with repeated conditional measurements

Quancheng Liu, Klaus Ziegler, David A Kessler, Eli Barkai

We investigate the effect of conditional null measurements on a quantum system and find a rich variety of behaviors. Specifically, quantum dynamics with a time independent in a finite dimensional Hilbert space are considered with repeated strong null measurements of a specified state. We discuss four generic behaviors that emerge in these monitored systems. The first arises in systems without symmetry, along with their associated degeneracies in the energy spectrum, and hence in the absence of dark states as well. In this case, a unique final state can be found which is determined by the largest eigenvalue of the survival operator, the non-unitary operator encoding both the unitary evolution between measurements and the measurement itself. For a three-level system, this is similar to the well known shelving effect. Secondly, for systems with built-in symmetry and correspondingly a degenerate energy spectrum, the null measurements dynamically select the degenerate energy levels, while the non-degenerate levels are effectively wiped out. Thirdly, in the absence of dark states, and for specific choices of parameters, two or more eigenvalues of the survival operator match in magnitude, and this leads to an oscillatory behavior controlled by the measurement rate and not solely by the energy levels. Finally, when the control parameters are tuned, such that the eigenvalues of the survival operator all coalesce to zero, one has exceptional points that corresponds to situations that violate the null measurement condition, making the conditional measurement process impossible.

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Apr 2021 • arXiv preprint arXiv:2104.10524

Observation of strong coupling between an inverse bowtie nano-antenna and a single j-aggregate

Adam Weissman, Maxim Shukharev, Adi Salomon

We demonstrate strong coupling between a single J-aggregate and an inverse bowtie plasmonic structure, when the J-aggregate is located at a specific axial distance from the metallic surface. Three hybrid modes are clearly observed, witnessing a strong interaction, with a Rabi splitting of up to 290 meV, the precise value of which significantly depends on the orientation of the J-aggregate with respect to the symmetry axis of the plasmonic structure. We repeated our experiments with a set of triangular hole arrays, showing consistent formation of three or more hybrid modes, in good agreement with numerical simulations.

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Apr 2021 • Microporous and Mesoporous Materials

Physicochemical evaluation of the effect of natural zeolite modification with didodecyldimethylammonium bromide on the adsorption of Bisphenol-A and Propranolol Hydrochloride

Akmaral B Rakhym, Gulziya A Seilkhanova, Yitzhak Mastai

Wastewater pollution by organic anions is of great interest. Surfactant-modified zeolites exhibit high adsorption of both organic and inorganic toxicants. Here, bisphenol-A and propranolol hydrochloride were adsorbed on natural zeolite modified with the cationic surfactant didodecyldimethylammonium bromide with and without pretreatment of the zeolite with NaCl and HCl. Detailed physicochemical analysis shows chemisorption, electrostatic and hydrophobic interactions with the surfactant and bisphenol-A, and in the case of propranolol, also physisorption.

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Apr 2021 • Batteries & Supercaps

Fluorination of Ni‐Rich Lithium‐Ion Battery Cathode Materials by Fluorine Gas: Chemistry, Characterization, and Electrochemical Performance in Full‐cells

Ulf Breddemann, Johannes Sicklinger, Florian Schipper, Victoria Davis, Anna Fischer, Korbinian Huber, Evan M Erickson, Michael Daub, Anke Hoffmann, Christoph Erk, Boris Markovsky, Doron Aurbach, Hubert A Gasteiger, Ingo Krossing

The mild fluorination of Ni‐rich NCM CAMs (NCM=nickel‐cobalt‐manganese oxide; CAM=cathode active material) with a few hundred mbar of elementary fluorine gas (F2) at room temperature was systematically studied. The resulting fluorinated CAMs were fully analyzed and compared to the pristine ones. Fluorination at room temperature converts part of the soluble basic species on the CAM‐surface into a protecting thin and amorphous LiF film. No formation of a metal fluoride other than LiF was detected. SEM images revealed a smoothened CAM surface upon fluorination, possibly due to the LiF film formation. Apparently due to this protecting, but insulating LiF‐film, the fluorinated material has a reduced electrical conductivity in comparison to the pristine material. Yet, all fluorinated Ni‐rich NCM CAMs showed a considerably higher press density than the pristine material, which in addition increased with higher …

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