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Apr 2023 • Pharmaceutics 15 (5), 1329, 2023

Homology-Directed-Repair-Based Genome Editing in HSPCs for the Treatment of Inborn Errors of Immunity and Blood Disorders

Daniel Allen, Nechama Kalter, Michael Rosenberg, Ayal Hendel

Genome engineering via targeted nucleases, specifically CRISPR-Cas9, has revolutionized the field of gene therapy research, providing a potential treatment for diseases of the blood and immune system. While numerous genome editing techniques have been used, CRISPR-Cas9 homology-directed repair (HDR)-mediated editing represents a promising method for the site-specific insertion of large transgenes for gene knock-in or gene correction. Alternative methods, such as lentiviral/gammaretroviral gene addition, gene knock-out via non-homologous end joining (NHEJ)-mediated editing, and base or prime editing, have shown great promise for clinical applications, yet all possess significant drawbacks when applied in the treatment of patients suffering from inborn errors of immunity or blood system disorders. This review aims to highlight the transformational benefits of HDR-mediated gene therapy and possible solutions for the existing problems holding the methodology back. Together, we aim to help bring HDR-based gene therapy in CD34+ hematopoietic stem progenitor cells (HSPCs) from the lab bench to the bedside.

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Apr 2023 • Photonics

Quantitative Phase Contrast Microscopy with Optimized Partially Coherent Illumination

Kequn Zhuo, Yang Wang, Ying Ma, Sha An, Zeev Zalevsky, Juanjuan Zheng, Peng Gao

This paper presents a partially coherent illumination quantitative phase contrast microscopic (PCI-QPCM) prototype. In the PCI-QPCM prototype, the light scattered by a rotating diffuser is coupled into a multi-mode fiber, and the output light is used as the illumination for PCI-QPCM. The illumination wave has a constrained spectrum with a diameter of tens of micrometers, which can reduce speckle noise and will not broaden the dc term of the object wave. In the Fourier plane of the object wave, grating-masked phase shifters generated by a spatial light modulator (SLM) allow for measuring the intensity of the undiffracted and diffracted components of the object wave, as well as the phase-shifted interference patterns of the two. Quantitative phase images can be reconstructed from the recorded intensity images. The proposed PCI-QPCM was demonstrated with quantitative phase imaging of a transparent waveguide and a phase-step sample.

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Apr 2023 • arXiv preprint arXiv:2304.14482

ULTRASAT: A wide-field time-domain UV space telescope

Y Shvartzvald, E Waxman, A Gal-Yam, EO Ofek, S Ben-Ami, D Berge, M Kowalski, R Bühler, S Worm, JE Rhoads, I Arcavi, D Maoz, D Polishook, N Stone, B Trakhtenbrot, M Ackermann, O Aharonson, O Birnholtz, D Chelouche, D Guetta, N Hallakoun, A Horesh, D Kushnir, T Mazeh, J Nordin, A Ofir, S Ohm, D Parsons, A Pe'er, HB Perets, V Perdelwitz, D Poznanski, I Sadeh, I Sagiv, S Shahaf, M Soumagnac, L Tal-Or, J Van Santen, B Zackay, O Guttman, P Rekhi, A Townsend, A Weinstein, I Wold

The Ultraviolet Transient Astronomy Satellite (ULTRASAT) is scheduled to be launched to geostationary orbit in 2026. It will carry a telescope with an unprecedentedly large field of view (204 deg) and NUV (230-290nm) sensitivity (22.5 mag, 5, at 900s). ULTRASAT will conduct the first wide-field survey of transient and variable NUV sources and will revolutionize our ability to study the hot transient universe: It will explore a new parameter space in energy and time-scale (months long light-curves with minutes cadence), with an extra-Galactic volume accessible for the discovery of transient sources that is 300 times larger than that of GALEX and comparable to that of LSST. ULTRASAT data will be transmitted to the ground in real-time, and transient alerts will be distributed to the community in 15 min, enabling a vigorous ground-based follow-up of ULTRASAT sources. ULTRASAT will also provide an all-sky NUV image to 23.5 AB mag, over 10 times deeper than the GALEX map. Two key science goals of ULTRASAT are the study of mergers of binaries involving neutron stars, and supernovae: With a large fraction (50%) of the sky instantaneously accessible, fast (minutes) slewing capability and a field-of-view that covers the error ellipses expected from GW detectors beyond 2025, ULTRASAT will rapidly detect the electromagnetic emission following BNS/NS-BH mergers identified by GW detectors, and will provide continuous NUV light-curves of the events; ULTRASAT will provide early (hour) detection and continuous high (minutes) cadence NUV light curves for hundreds of core-collapse supernovae, including for rarer supernova …

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Apr 2023 • Optics Continuum

Designing an optical phase element for field of view enhancement by using wavelength multiplexing

Vismay Trivedi, Abhijit Sanjeev, Zeev Zalevsky

Enhancing the image quality of the captured image is one of the prime objectives of modern image acquisition systems. These imaging systems can be broadly divided into two subsystems: an optical subsystem and a digital subsystem. There are various limitations associated with the optical and digital subsystems. One of the crucial parameters that are affected by the limitation of the physical extent of the recording or capturing system is the field of view (FOV). A reduced FOV can lead to loss of information thereby increasing the time for post-processing of images as well as introducing mechanical scanning to achieve a larger FOV. A simple yet efficient technique for FOV enhancement is demonstrated in this paper. An optical element is designed in such a way that it diffracts different wavelengths in the desired manner and the information from different regions of the object is carried by different wavelengths which …

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Apr 2023 • MRS Bulletin, 2023

In remembrance: George Crabtree (1944-2023)

Elizabeth Kócs, David Cahen, Dave Ginley

A stunning loss to the scientific community and to humanity, the news of George Crabtree’s recent demise came as a shock to his numerous colleagues and friends. George was the epitome of an inspirational visionary and an astounding human being, as well as a force for critical and interdisciplinary scientific thought. Remembered by all as approachable, warm, wonderful, kind, curious, fearless, insightful, articulate, inspiring, inclusive, empathetic, intelligent, and impactful, George was the consummate scientist, gentleman, and leader with a deep appreciation for diverse thought, dialogue, and approaches. With so many dimensions to George, we will always remember him as our friend, a thoughtful scholar, a kind soul, and for his smile and laugh. His sudden recent death on January 23, 2023 affected many of us individually and impacted the entire materials research community. George’s immense contributions to …

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Mar 2023 • Advanced Materials Interfaces

Scanning SQUID Imaging of Reduced Superconductivity Due to the Effect of Chiral Molecule Islands Adsorbed on Nb

Meital Ozeri, TR Devidas, Hen Alpern, Eylon Persky, Anders V Bjorlig, Nir Sukenik, Shira Yochelis, Angelo Di Bernardo, Beena Kalisky, Oded Millo, Yossi Paltiel

Unconventional superconductivity was realized in systems comprising a monolayer of magnetic adatoms adsorbed on conventional superconductors, forming Shiba‐bands. Another approach to induce unconventional superconductivity and 2D Shiba‐bands was recently introduced, namely, by adsorbing chiral molecules (ChMs) on conventional superconductors, which act in a similar way to magnetic impurities as verified by conductance spectroscopy. However, the fundamental effect ChMs have on the strength of superconductivity has not yet been directly observed and mapped. In this work, local magnetic susceptometry is applied on heterostructures comprising islands of ChMs (α‐helix L‐polyalanine) monolayers adsorbed on Nb. It is found that the ChMs alter the superconducting landscape, resulting in spatially‐modulated weaker superconductivity. Surprisingly, the reduced diamagnetic response is located …

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Mar 2023 • Physical Review A

Coherence and realism in the Aharonov-Bohm effect

Ismael L Paiva, Pedro R Dieguez, Renato M Angelo, Eliahu Cohen

The Aharonov-Bohm effect is a fundamental topological phenomenon with a wide range of applications. It consists of a charge encircling a region with a magnetic flux in a superposition of wave packets having their relative phase affected by the flux. In this work we analyze this effect using an entropic measure known as realism, originally introduced as a quantifier of a system's degree of reality and mathematically related to notions of global and local quantum coherence. More precisely, we look for observables that lead to gauge-invariant realism associated with the charge before it completes its loop. We find that the realism of these operators has a sudden change when the line connecting the center of both wave packets crosses the solenoid. Moreover, we consider the case of a quantized magnetic-field source, pointing out similarities and differences between the two cases. Finally, we discuss some …

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Mar 2023 • Society of Photo-Optical Instrumentation Engineers (SPIE) Conference Series

Wavelengths encoded illumination for resolution enhancement and imaging beyond scattering medium

Omer Wagner, Asaf Shahmoon, Zeev Zalevsky

In this paper a wavelength-multiplexing based super-resolving concept is presented to allow high resolution imaging through blood. We use temporally pulsed and spectrally wide-band laser while at its output we have special grating and a spatial 2-D transmission mask allowing to project wavelengths' dependent high-resolution spatial orthogonal encoding patterns (different spatial patterns for each wavelength). The ballistic photons of the short temporal pulses allow the high-resolution encoding pattern to reach the inspected object through the scattering blood medium without being spatially blurred. The light is intentionally collected via low resolution optics. The high-resolution reconstruction can be obtained digitally by post processing or optically by passing the collected low-resolution data through a similar grating and 2-D mask which do an all-optical decoding. After summing all the images together, the super …

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Mar 2023 • Cellular and Molecular Gastroenterology and Hepatology

High-Resolution Genomic Profiling of Liver Cancer Links Etiology With Mutation and Epigenetic Signatures

Shira Perez, Anat Lavi-Itzkovitz, Moriah Gidoni, Tom Domovitz, Roba Dabour, Ishant Khurana, Ateret Davidovich, Ana Tobar, Alejandro Livoff, Evgeny Solomonov, Yaakov Maman, Assam El-Osta, Yishan Tsai, Ming-Lung Yu, Salomon M Stemmer, Izhak Haviv, Gur Yaari, Meital Gal-Tanamy

BackgroundHepatocellular carcinoma (HCC) is a model of diverse spectrum of cancers, since it is induced by well-known etiologies, mainly Hepatitis C virus (HCV) and Hepatitis B virus (HBV). Here we aimed to identify HCV-specific mutational signature and explored the link between the HCV-related regional variation in mutations rates and HCV-induced alterations in genome-wide chromatin organization.MethodsTo identify an HCV-specific mutational signature in HCC, we performed high-resolution targeted sequencing to detect passenger mutations on 64 HCC samples from three etiology groups – HBV, HCV, or other. To explore the link between genomic signature and genome-wide chromatin organization we performed ChIP-seq for the transcriptionally permissive H3K4me3, H3K9ac and suppressive H3K9me3 modifications following HCV infection.ResultsRegional variation in mutations rates analysis …

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Mar 2023 • Science 379 (6637), eade1220, 2023

Geometric deep optical sensing

Shaofan Yuan, Chao Ma, Ethan Fetaya, Thomas Mueller, Doron Naveh, Fan Zhang, Fengnian Xia

Geometry, an ancient yet vibrant branch of mathematics, has important and far-reaching impacts on various disciplines such as art, science, and engineering. Here, we introduce an emerging concept dubbed “geometric deep optical sensing” that is based on a number of recent demonstrations in advanced optical sensing and imaging, in which a reconfigurable sensor (or an array thereof) can directly decipher the rich information of an unknown incident light beam, including its intensity, spectrum, polarization, spatial features, and possibly angular momentum. We present the physical, mathematical, and engineering foundations of this concept, with particular emphases on the roles of classical and quantum geometry and deep neural networks. Furthermore, we discuss the new opportunities that this emerging scheme can enable and the challenges associated with future developments.

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Mar 2023 • Real-time Measurements, Rogue Phenomena, and Single-Shot Applications VIII …, 2023

Quantum interferometer based on time-lenses

Sara Meir, Eliahu Cohen, Moti Fridman

Time-lenses can image ultrafast signals in time. Placing them in a 2-f configuration leads to Fourier transform of the input signal and ultrafast spectroscopy. We utilized two time-lenses in a 4-f configuration and formed an interferometer in the time domain. Our time lenses are based on four-wave mixing process, generating an idler beam which serves as the output. The output from the first time-lens is the input to the second time-lens. At the output of the second time-lens, we get an interference between the signal beams of both time-lenses and the idler beams of both time-lenses. This interference is sensitive to ultrafast phase shifts in time and can lead to interfere signals in different times. This interferometer is good for quantum imaging, and studying the temporal structure of entangled photons. In this talk we will demonstrate the interferometer, how we exploit time-lenses for interferometry, the application of the …

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Mar 2023 • Proc. of SPIE Vol

Dynamics and Fluctuations in Biomedical Photonics XX

Valery V Tuchin, Martin J Leahy, Ruikang K Wang, Zeev Zalevsky

PROCEEDINGS OF SPIE Page 1 PROCEEDINGS OF SPIE SPIEDigitalLibrary.org/conference-proceedings-of-spie Front Matter: Volume 12378 , "Front Matter: Volume 12378," Proc. SPIE 12378, Dynamics and Fluctuations in Biomedical Photonics XX, 1237801 (31 March 2023); doi: 10.1117/12.2676834 Event: SPIE BiOS, 2023, San Francisco, California, United States Downloaded From: https://www.spiedigitallibrary.org/conference-proceedings-of-spie on 07 Apr 2023 Terms of Use: https://www.spiedigitallibrary.org/terms-of-use Page 2 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 …

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Mar 2023 • arXiv preprint arXiv:2303.00701

Time-symmetry and topology of the Aharonov-Bohm effect

Yakir Aharonov, Ismael L Paiva, Zohar Schwartzman-Nowik, Avshalom C Elitzur, Eliahu Cohen

The Aharonov-Bohm (AB) effect has been highly influential in fundamental and applied physics. Its topological nature commonly implies that an electron encircling a magnetic flux source in a field-free region must close the loop in order to generate an observable effect. In this Letter, we study a variant of the AB effect that apparently challenges this concept. The significance of weak values and nonlocal equations of motion is discussed as part of the analysis, shedding light on and connecting all these fundamental concepts.

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Mar 2023 • Real-time Measurements, Rogue Phenomena, and Single-Shot Applications VIII …, 2023

Quantum temporal optics

Moti Fridman

Temporal optics, and specifically time-lenses and time-stretch systems, revolutionized the field of ultrafast measurements. Over the last years, we utilized time-lenses to measure different quantum schemes and studied the temporal modes of correlated photons with high temporal resolution. We developed temporal schemes based on quantum light, for realizing quantum tomography in the time-domain. We developed low-resolution time-lenses for weak quantum measurements. Finally, we suggest how quantum time-lens can lead to optical deep learning systems. In the talk, I will give an overview of the different types of quantum temporal schemes, elaborate on the future challenges in the field, and discuss the prospects and future applications which may be possible.

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Mar 2023 • Nanoscale and Quantum Materials: From Synthesis and Laser Processing to …, 2023

Laser induced transfer of 2D materials for optoelectronic applications

I Cheliotis, A Logotheti, F Zacharatos, A Pesquera, A Zurutuza, D Naveh, L Tsetseris, I Zergioti

The advent of functional devices based on two-dimensional (2D) materials has further intensified the interest in the latter. However, the fabrication of structures using layered materials remains a key challenge. Recently, we proposed the so-called “Laser-Induced Transfer” method (LIT), as a digital and solvent-free approach for the high-resolution and intact transfer of 2D materials’ pixels. Here, we will further highlight the versatility of LIT by reporting results on the high-quality digital transfer of graphene and MoS2. These materials have emerged in the field of nanoelectronics, sensors and photonics due to their unique optoelectronic properties, but their high-quality transfer remains a hurdle. The quality of the transferred films has been confirmed with systematic characterization based on Scanning Electron Microscopy and Raman spectroscopy, as well as mobility’s extraction. Then we will present how the laser …

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Mar 2023 • The Journal of Physical Chemistry Letters

Protein Orientation Defines Rectification of Electronic Current via Solid-State Junction of Entire Photosystem-1 Complex

Jerry A Fereiro, Tatyana Bendikov, Andreas Herrmann, Israel Pecht, Mordechai Sheves, David Cahen

We demonstrate that the direction of current rectification via one of nature’s most efficient light-harvesting systems, the photosystem 1 complex (PS1), can be controlled by its orientation on Au substrates. Molecular self-assembly of the PS1 complex using four different linkers with distinct functional head groups that interact by electrostatic and hydrogen bonds with different surface parts of the entire protein PS1 complex was used to tailor the PS1 orientation. We observe an orientation-dependent rectification in the current–voltage characteristics for linker/PS1 molecule junctions. Results of an earlier study using a surface two-site PS1 mutant complex having its orientation set by covalent binding to the Au substrate supports our conclusion. Current–voltage–temperature measurements on the linker/PS1 complex indicate off-resonant tunneling as the main electron transport mechanism. Our ultraviolet photoemission …

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Mar 2023 • PLoS Genetics

Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms

Adi Avram-Shperling, Eli Kopel, Itamar Twersky, Orshay Gabay, Amit Ben-David, Sarit Karako-Lampert, Joshua JC Rosenthal, Erez Y Levanon, Eli Eisenberg, Shay Ben-Aroya

The most abundant form of RNA editing in metazoa is the deamination of adenosines into inosines (A-to-I), catalyzed by ADAR enzymes. Inosines are read as guanosines by the translation machinery, and thus A-to-I may lead to protein recoding. The ability of ADARs to recode at the mRNA level makes them attractive therapeutic tools. Several approaches for Site-Directed RNA Editing (SDRE) are currently under development. A major challenge in this field is achieving high on-target editing efficiency, and thus it is of much interest to identify highly potent ADARs. To address this, we used the baker yeast Saccharomyces cerevisiae as an editing-naïve system. We exogenously expressed a range of heterologous ADARs and identified the hummingbird and primarily mallard-duck ADARs, which evolved at 40–42°C, as two exceptionally potent editors. ADARs bind to double-stranded RNA structures (dsRNAs), which in turn are temperature sensitive. Our results indicate that species evolved to live with higher core body temperatures have developed ADAR enzymes that target weaker dsRNA structures and would therefore be more effective than other ADARs. Further studies may use this approach to isolate additional ADARs with an editing profile of choice to meet specific requirements, thus broadening the applicability of SDRE.

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Mar 2023 • arXiv preprint arXiv:2003.01756

Electrostatic modulation of the lateral carrier density profile in field effect devices with nonlinear dielectrics

Eylon Persky, Hyeok Yoon, Yanwu Xie, Harold Y Hwang, Jonathan Ruhman, Beena Kalisky

We study the effects of electrostatic gating on the lateral distribution of charge carriers in two dimensional devices, in a non-linear dielectric environment. We compute the charge distribution using the Thomas-Fermi approximation to model the electrostatics of the system. The electric field lines generated by the gate are focused at the edges of the device, causing an increased depletion near the edges, compared to the center of the device. This effect strongly depends on the dimensions of the device, and the non-linear dielectric constant of the substrate. We experimentally demonstrate this effect using scanning superconducting interference device (SQUID) microscopy images of current distributions in gated LaAlO/SrTiO heterostructures.

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Mar 2023 • Science 379 (6637), eade1220, 2023

Geometric deep optical sensing

Shaofan Yuan, Chao Ma, Ethan Fetaya, Thomas Mueller, Doron Naveh, Fan Zhang, Fengnian Xia

Geometry, an ancient yet vibrant branch of mathematics, has important and far-reaching impacts on various disciplines such as art, science, and engineering. Here, we introduce an emerging concept dubbed “geometric deep optical sensing” that is based on a number of recent demonstrations in advanced optical sensing and imaging, in which a reconfigurable sensor (or an array thereof) can directly decipher the rich information of an unknown incident light beam, including its intensity, spectrum, polarization, spatial features, and possibly angular momentum. We present the physical, mathematical, and engineering foundations of this concept, with particular emphases on the roles of classical and quantum geometry and deep neural networks. Furthermore, we discuss the new opportunities that this emerging scheme can enable and the challenges associated with future developments.

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Mar 2023 • Bulletin of the American Physical Society

Zwitterists: Photo-patternable Polymer Zwitterions for Interfacial Dipole Doping of Monolayer Graphene

James Nicolas Pagaduan, Nicholas Hight-Huf, Yehiel Nagar, Le Zhou, Avdhoot Datar, Doron Naveh, Michael Barnes, Ashwin Ramasubramaniam, Reika Katsumata, Todd Emrick

K04. 00003: Zwitterists: Photo-patternable Polymer Zwitterions for Interfacial Dipole Doping of Monolayer Graphene*

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Mar 2023 • The Journal of Physical Chemistry Letters

Excitation Intensity-Dependent Quantum Yield of Semiconductor Nanocrystals

Subhabrata Ghosh, Ulrich Ross, Anna M Chizhik, Yung Kuo, Byeong Guk Jeong, Wan Ki Bae, Kyoungwon Park, Jack Li, Dan Oron, Shimon Weiss, Jörg Enderlein, Alexey I Chizhik

One of the key phenomena that determine the fluorescence of nanocrystals is the nonradiative Auger-Meitner recombination of excitons. This nonradiative rate affects the nanocrystals’ fluorescence intensity, excited state lifetime, and quantum yield. Whereas most of the above properties can be directly measured, the quantum yield is the most difficult to assess. Here we place semiconductor nanocrystals inside a tunable plasmonic nanocavity with subwavelength spacing and modulate their radiative de-excitation rate by changing the cavity size. This allows us to determine absolute values of their fluorescence quantum yield under specific excitation conditions. Moreover, as expected considering the enhanced Auger-Meitner rate for higher multiple excited states, increasing the excitation rate reduces the quantum yield of the nanocrystals.

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