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Mar 2022 • Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XX …, 2022

Characterization of a large gated SPAD array for in vivo fluorescence lifetime imaging of drug target engagement

Jason T Smith, Alena Rudkouskaya, Shan Gao, Arin Ulku, Claudio Bruschini, Edoardo Charbon, Shimon Weiss, Margarida Barroso, Xavier Intes, Xavier Michalet

Near-Infrared wide-field Fluorescence Lifetime Imaging (FLI) has become an increasingly popular method due to its unique specificity in sensing the cellular micro-environment and/or protein-protein interactions via FRET, but the approach is still challenging due to inefficient detection modules. Here, we report on the characterization of a large gated SPAD array, SwissSPAD2, towards in vivo preclinical imaging of FLI-FRET. Fluorescence decay fitting as well as phasor analysis are used to demonstrate the ability of SwissSPAD2 to accurately quantify short lifetimes and associated lifetime parameters in both in vitro and in vivo experiments, in full agreement with gated ICCD measurements.

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Mar 2022 • Polymers for Advanced Technologies

Chirality of proteinoid nanoparticles made of lysine and phenylalanine

Liroy Lugasi, Gil Otis, Matan Oliel, Shlomo Margel, Yitzhak Mastai


Mar 2022 • ACS Energy Letters

Stabilizing High-Voltage Lithium-Ion Battery Cathodes Using Functional Coatings of 2D Tungsten Diselenide

Sandipan Maiti, Rajashree Konar, Hadar Sclar, Judith Grinblat, Michael Talianker, Maria Tkachev, Xiaohan Wu, Aleksandr Kondrakov, Gilbert Daniel Nessim, Doron Aurbach

Functional surface coatings were applied on high voltage spinel (LiNi0.5Mn1.5O4; LNMO) and Ni-rich (LiNi0.85Co0.1Mn0.05O2; NCM851005) NCM cathode materials using few-layered 2H tungsten diselenide (WSe2). Simple liquid-phase mixing with WSe2 in 2-propanol and low-temperature (130 °C) heat treatment in nitrogen flow dramatically improved electrochemical performance, including stable cycling, high-rate performance, and lower voltage hysteresis in Li coin cells at 30 and 55 °C. Significantly improved capacity retention at 30 °C [Q401/Q9 of 99% vs 38% for LNMO and Q322/Q23 of 64% vs 46% for NCM851005] indicated efficient functionality. TEM and XPS clarified the coating distribution and coordination with the cathode surface, while postcycling studies revealed its sustainability, enabling lower transition metal dissolution and minor morphological deformation/microcrack formation. A modified and …

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Mar 2022 • Bulletin of the American Physical Society

MoS2 Hybrids with Intercalated Zerovalent Metals for Optoelectronics

Ashwin Ramasubramaniam, Chen Stern, Avraham Twitto, Rafi Snitkoff, Yafit Fleger, Sabyasachi Saha, Loukya Bodipatti, Akash Jain, Mengjing Wang, Kristie Koski, Francis Deepak, Doron Naveh

The intercalation of layered compounds is a promising route for scalable synthesis of 2D heterostructures with novel emergent optoelectronic properties. Here, we investigate, via first principles calculations, the intercalation of zerovalent metals within the van der Waals gap of bulk MoS 2. Specifically, we focus on a novel Cu-MoS 2 hybrid that accommodates uniform, continuous 2D layers of metallic Cu within the vdW gap of MoS 2. We study the evolution of the Cu-MoS 2 hybrid with increasing Cu content and examine the consequences for intercalation energetics and optoelectronic properties as the intercalated Cu evolves from disordered clusters to contiguous layers. We identify an emergent plasmon resonance (~ 1eV) that is unique to the Cu-MoS 2 hybrid, arising from resonant 2D Cu states within the MoS 2 band gap. Our calculations are shown to be in good agreement with experiments and help explain the …

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Mar 2022 • Nature Communications

Landscape of adenosine-to-inosine RNA recoding across human tissues

Orshay Gabay, Yoav Shoshan, Eli Kopel, Udi Ben-Zvi, Tomer D Mann, Noam Bressler, Roni Cohen‐Fultheim, Amos A Schaffer, Shalom Hillel Roth, Ziv Tzur, Erez Y Levanon, Eli Eisenberg

RNA editing by adenosine deaminases changes the information encoded in the mRNA from its genomic blueprint. Editing of protein-coding sequences can introduce novel, functionally distinct, protein isoforms and diversify the proteome. The functional importance of a few recoding sites has been appreciated for decades. However, systematic methods to uncover these sites perform poorly, and the full repertoire of recoding in human and other mammals is unknown. Here we present a new detection approach, and analyze 9125 GTEx RNA-seq samples, to produce a highly-accurate atlas of 1517 editing sites within the coding region and their editing levels across human tissues. Single-cell RNA-seq data shows protein recoding contributes to the variability across cell subpopulations. Most highly edited sites are evolutionary conserved in non-primate mammals, attesting for adaptation. This comprehensive set can …

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Mar 2022 • Sciences

NIR fluorescence lifetime macroscopic imaging with a time-gated SPAD camera

X Michalet, A Ulku, J Smith, C Bruschini, S Weiss

The performance of SwissSPAD2 (SS2), a large scale, widefield time-gated CMOS SPAD imager developed for fluorescence lifetime imaging, has recently been described in the context of visible range and fluorescence lifetime imaging microscopy (FLIM) of dyes with lifetimes in the 2.5–4 ns range. Here, we explore its capabilities in the NIR regime relevant for small animal imaging, where its sensitivity is lower and typical NIR fluorescent dye lifetimes are much shorter (1 ns or less). We carry out this study in a simple macroscopic imaging setup based on a compact NIR picosecond pulsed laser, an engineered diffuser-based illumination optics, and NIR optimized imaging lens suitable for well-plate or small animal imaging. Because laser repetition rates can vary between models, but the synchronization signal frequency accepted by SS2 is fixed to 20 MHz, we first checked that a simple frequency-division scheme …

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Mar 2022 • arXiv preprint arXiv:2203.00688

High-resolution absorption measurements with free-electron lasers using ghost spectroscopy

Yishai Klein, Edward Strizhevsky, Flavio Capotondi, Dario De Angelis, Luca Giannessi, Matteo Pancaldi, Emanuele Pedersoli, Giuseppe Penco, Kevin C Prince, Or Sefi, Young Yong Kim, Ivan A Vartanyants, Sharon Shwartz

We demonstrate a simple and robust high-resolution ghost spectroscopy approach for x-ray and extreme ultraviolet absorption spectroscopy at free-electron laser sources. Our approach requires an on-line spectrometer before the sample and a downstream bucket detector. We use this method to measure the absorption spectrum of silicon, silicon carbide and silicon nitride membranes in the vicinity of the silicon L2,3-edge. We show that ghost spectroscopy allows the high-resolution reconstruction of the sample spectral response using a coarse energy scan with self-amplified spontaneous emission radiation. For the conditions of our experiment the energy resolution of the ghost-spectroscopy reconstruction is higher than the energy resolution reached by scanning the energy range by narrow spectral bandwidth radiation produced by the seeded free-electron laser. When we set the photon energy resolution of the ghost spectroscopy to be equal to the resolution of the measurement with the seeded radiation, the measurement time with the ghost spectroscopy method is shorter than scanning the photon energy with seeded radiation. The exact conditions for which ghost spectroscopy can provide higher resolution at shorter times than measurement with narrow band scans depend on the details of the measurements and on the properties of the samples and should be addressed in future studies.

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Mar 2022 • Inorganics

Improved Electrochemical Behavior and Thermal Stability of Li and Mn-Rich Cathode Materials Modified by Lithium Sulfate Surface Treatment

Hadar Sclar, Sandipan Maiti, Rosy Sharma, Evan M Erickson, Judith Grinblat, Ravikumar Raman, Michael Talianker, Malachi Noked, Aleksandr Kondrakov, Boris Markovsky, Doron Aurbach


Mar 2022 • High Contrast Metastructures XI, PC120110H, 2022

High-index topological insulator nanostructures for mid-infrared meta-optics

Sukanta Nandi, Danveer Singh, Pilkhaz Pilkhaz Nanikashvili, Shany Cohen, Doron Naveh, Tomer Lewi

Topological insulators (TIs) are a new class of condensed matter system that host topologically protected surface states, leading to dissipationless electron transport. This intrinsic characteristic makes them potential candidate for quantum computing owing to their ability to preserve quantum coherence. Recently, these systems and the concept of topology have been embraced by the photonics community as well. In this work, we study the mid-infrared optical properties of high index (n~5.2) TI bismuth selenide (Bi2Se3) nanobeams (NBs), grown by chemical vapor deposition. Using Finite-difference time-domain (FDTD) simulations and FTIR nanospectroscopy, we find that these NBs support size-tunable Mie-resonant modes across the infrared (~1-16 µm). Furthermore, polarized measurements reveal that the total optical response of these deep subwavelength NBs is composed of TE and TM resonant mode. Finally …

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Mar 2022 • Bulletin of the American Physical Society

Electronic Tuning of 2D Materials with Zwitterionic and Functional Polymers

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

Functional polymers are increasingly recognized for their ability to engineer the electronic properties of 2D materials for device performance enhancement. Although dipole-rich polymer zwitterions have shown significant work function modulation of 2D materials, the contribution of zwitterion structure is not well understood. To this end, a series of zwitterionic sulfobetaine-based random copolymers with varying substituents has been prepared and applied as negative-tone resists on graphene, enabling evaluation of surface potential contrast. The influence of steric footprint on calculated dipole moment and resulting work function measured by ultraviolet photoelectron spectroscopy will be presented. To assess the nature of graphene surface doping by polymer zwitterions, a sample geometry that permits direct access to either the polymer or graphene side is employed using a zwitterionic phosphorylcholine-based …

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Mar 2022 • ACS Applied Energy Materials

Combinatorial Synthesis and Screening of a Ternary NiFeCoOx Library for the Oxygen Evolution Reaction

A Usha Vijayakumar, N Aloni, V Thazhe Veettil, G Rahamim, SS Hardisty, M Zysler, S Tirosh, D Zitoun

The development of an efficient catalyst for the oxygen evolution reaction (OER) is critical to fulfilling the mission of hydrogen generation by water splitting. Various multicomponent systems have been investigated so far for the OER, although a systematic investigation is lacking and there are discrepancies as to which formulations make the best catalyst. Here, we perform a systematic investigation of a ternary Ni-Fe-Co oxide gradient library for the OER, using a combinatorial approach. This approach allows a much faster investigation of a vast compositional space compared to the traditional step by step approach. Also, it enables a more reliable comparison of the various catalysts as they all experience the same process and measurement conditions. We used the spray pyrolysis technique in combinatorial electrocatalyst screening for the first time for the generation of a gradient library of Ni-Fe-Co oxides …

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Mar 2022 • High Contrast Metastructures XI, PC120110H, 2022

High-index topological insulator nanostructures for mid-infrared meta-optics

Sukanta Nandi, Danveer Singh, Pilkhaz Pilkhaz Nanikashvili, Shany Cohen, Doron Naveh, Tomer Lewi

Topological insulators (TIs) are a new class of condensed matter system that host topologically protected surface states, leading to dissipationless electron transport. This intrinsic characteristic makes them potential candidate for quantum computing owing to their ability to preserve quantum coherence. Recently, these systems and the concept of topology have been embraced by the photonics community as well. In this work, we study the mid-infrared optical properties of high index (n~5.2) TI bismuth selenide (Bi2Se3) nanobeams (NBs), grown by chemical vapor deposition. Using Finite-difference time-domain (FDTD) simulations and FTIR nanospectroscopy, we find that these NBs support size-tunable Mie-resonant modes across the infrared (~1-16 µm). Furthermore, polarized measurements reveal that the total optical response of these deep subwavelength NBs is composed of TE and TM resonant mode. Finally …

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Mar 2022 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XIX …, 2022

Golden exosomes: a new platform for cancer theranostics

Adi Anaki, Oshra Betzer, Menachem Motiei, Tamar Sadan, Dror Fixler, Rachela Popovtzer

Delivery of therapeutics to tumors is a major challenge, due to the sequence of formidable biological barriers in the body and tumor, which limit the penetration of various nano-carriers and drugs into the tumor. Exosomes are promising vectors for delivery of anti-tumor therapies, due to their biocompatibility, ability to evade clearance, and innate ability to home to, and interact with, target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome bio-distribution, tumor targeting, and the ability to overcome tumor barriers. Here, we examined these parameters using mesenchymal stem cell (MSCs)-derived exosomes loaded with gold nanoparticles (GNPs), aiming to delineate design principles for therapy loading and delivery. This novel technology provides essential and fundamental knowledge on exosomes for enhanced targeted drug …

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Mar 2022 • PLoS pathogens

Experimental evolution links post-transcriptional regulation to Leishmania fitness gain

Laura Piel, K Shanmugha Rajan, Giovanni Bussotti, Hugo Varet, Rachel Legendre, Caroline Proux, Thibaut Douché, Quentin Giai-Gianetto, Thibault Chaze, Thomas Cokelaer, Barbora Vojtkova, Nadav Gordon-Bar, Tirza Doniger, Smadar Cohen-Chalamish, Praveenkumar Rengaraj, Céline Besse, Anne Boland, Jovana Sadlova, Jean-François Deleuze, Mariette Matondo, Ron Unger, Petr Volf, Shulamit Michaeli, Pascale Pescher, Gerald F Späth

The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth in promastigote culture (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network associated with parasite fitness gain, with genome instability causing highly reproducible, gene dosage-independent and -dependent changes. Reduction of flagellar transcripts and increase in coding and non-coding RNAs implicated in ribosomal biogenesis and protein translation were not correlated to dosage changes of the corresponding genes, revealing a gene dosage-independent, post-transcriptional mechanism of regulation. In contrast, abundance of gene products implicated in post-transcriptional regulation itself correlated to corresponding gene dosage changes. Thus, RNA abundance during parasite adaptation is controled by direct and indirect gene dosage changes. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification …

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Mar 2022 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XIX …, 2022

Scattering detection in multi-layer tissue: phantom experiments and in vivo applications

Inbar Yariv, Hamootal Duadi, Dror Fixler

Deep tissue imaging using visible light is challenging due to its turbid nature. Nevertheless, clinical information can be detected by sensing changes in the tissue’s optical properties with low spatial resolution. The most challenging aspect is the spectral dependent scattering, which varies with physiological state and tissue layer. In this paper, we present the multi-layer study of the reflection-based iterative multiplane optical property extraction (IMOPE) technique. The IMOPE is a noninvasive nanophotonics technique that detects medium scattering properties based on the reemitted light phase. The extracted scattering properties are used as indicators of the internal tissue information and the presence of additional nanoparticles (NPs) in it. The technique is a combination of a theoretical model, an experimental setup, and the phase retrieval Gerchberg-Saxton algorithm. The IMOPE experimental setup records light …

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Mar 2022 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XIX …, 2022

Designing a quantifiable detection method for the optimization of gold nanoparticle based gene therapy

Jacqueline Labovitz, Menachem Motiei, Tamar Sadan, Dror Fixler, Rachela Popovtzer


Mar 2022 • Optical and Quantum Sensing and Precision Metrology II, PC120160Z, 2022

Nonlinear quantum interferometer in the time and frequency domains

Moti Fridman, Eliahu Cohen

Interferometers are highly sensitive to phase differences and are utilized in numerous schemes. Quantum interferometers are able to improve the sensitivity of classical interferometers beyond the shot-noise limit. This is done by employing squeezed states of light and destructive interference of the noise in the system. We developed a quantum SU(1,1) interferometer in the time domain. Our nonlinear quantum interferometer creates interference of the input signals at different times and frequencies. We can control the time and frequency differences for investigating the full temporal and spectral structure of the signal. This quantum interferometer can be utilized for sensing ultrafast phase changes, quantum imaging, temporal mode encoding, and studying the temporal structure of entangled photons.

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Mar 2022 • Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XIX …, 2022

Extracting the reduced scattering coefficient in different optical magnifications in the blue regime: theory and experiments

Channa Shapira, Inbar Yariv, Hamootal Duadi, Dror Fixler

Imaging inside a turbid media is range limited. In contrast, sensing the medium’s optical properties is possible in larger depths using the iterative multi-plane optical properties extraction (IMOPE) technique. It analyzes the reemitted light phase image reconstructed from the iterative multi-plane Gerchberg-Saxton (GS) algorithm. The root mean square (RMS) of the phase yields two graphs with opposite behaviors, that cross each other in μ's,cp. The graphs enable the extraction of the reduced scattering coefficient, μs', of the measured tissue. The IMOPE was originally developed for illumination of red wavelength and for biological applications and was extended to the blue regime of the electromagnetic field, which is applicable for underwater research. In this work, we aim to extend the range of μs' detection by optical magnification. We use a modified diffusion theory and show how μ's,cp shifts with the varying …

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Mar 2022 • Bulletin of the American Physical Society

One dimensional quantum Wigner crystals and SU (4) magnetism

Gergely Zarand, Shahal Ilani, Assaf Hamo, Catalin Pascu Moca, Örs Legeza, Ilanit Shapir, Sharon Pecker

The quantum crystal of electrons, predicted by Jenő Wigner almost 90 years ago, is one of the most elusive states of matter. In the very dilute limit, where the crystal forms, disorder effects and inhomogeneity very easily destroy this fragile state of matter, which is therefore very hard to be observed in its pristine form. It is also a major challenge for theorists to produce quantitative results in this strongly interacting, dilute limit, where the melting of the crystal occurs. We present corroborated experimental and theoretical results, which lead to a recent, direct observation of the spatial crystal structure of one dimensional Wigner quantum crystals in carbon nanotubes [1]. In the experiments, we a non-invasive single electron (hole) probe is employed, and we compare the experimental results with self-consistent DMRG simulations. We also investigate the tunneling of the crystal in a double well potential, and demonstrate by …

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Mar 2022 • Scientific Reports

Analysis of swallowing in infants and adults using speckle pattern analysis

Raz Shahmoon, Yitav Tamir, Yevgeny Beiderman, Sergey Agdarov, Yafim Beiderman, Zeev Zalevsky


Mar 2022 • International Journal of Molecular Sciences 23 (7), 3811, 2022

Behavioral Neuroscience in the Era of Genomics: Tools and Lessons for Analyzing High-Dimensional Datasets

Assa Bentzur, Shahar Alon, Galit Shohat-Ophir


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