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Mar 2023 • Bulletin of the American Physical Society

Measurement of Higher Order X-ray Optical Mixing

Chance Ornelas-Skarin, David Reis, Jerome Hastings, Mariano Trigo, Shambhu Ghimire, Daria Gorelova, Matthias Fuchs, Sharon Shwartz, Diling Zhu, Takahiro Sato, Quynh Nguyen, Tatiana Bezriadina, Henrik Lemke, Roman Mankowsky, Mathias Sander, Nelson Hua, Ludmila Diniz Leroy, Gilberto De La Pena

X-ray optical wave mixing is a nonlinear diffraction method that gives direct information about the Ångstrom and femtosecond-scale structure of the local optically-induced charge density in bulk solids, information unavailable to purely optical methods. The first measurements of wave mixing between x rays and optical photons were reported for single crystal diamond [Glover et al., Nature 488, 603 (2012)]. Here we report x-ray optical wave mixing experiments using the Swiss-FEL and LCLS hard x-ray free-electron lasers. To measure the wave-mixing signal we use silicon crystal optics to monochromate the free-electron laser output and analyze the energy-angle dependent wave-mixing signal while rejecting the elastic background. The results include the first measurements from silicon and the first measurement of the higher-order wave-mixing process generating the sum frequency of two optical and one x-ray …

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Mar 2023 • 2023 Optical Fiber Communications Conference and Exhibition (OFC), 1-3, 2023

Incoherent Fiber-based Optical Neuromorphic Computing Circuit

Maya Yevnin, Alon Harel, Or Arbel-Arenfrid, Zeev Zalevsky, Eyal Cohen

We present novel photonic neuromorphic computing scheme working with incoherent light while capable implementing negative weighting for the neural network and obtaining reliable/accurate computing of the linear multiply-accumulate function necessary for neural networks applications.

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Mar 2023 • Frontiers in Biological Detection: From Nanosensors to Systems XV, PC1239704, 2023

Improving the sensitivity of fluorescence-based immunoassays by time-resolved and spatial-resolved measurements (Conference Presentation)

Ran Kremer, Shira Roth, Avital Bross, Yair Noam, Amos Danielli

In fluorescence-based biosensing applications, to increase optical detection sensitivity, time-resolved measurements are extensively used. Magnetic modulation biosensing (MMB) is a novel, fast, and sensitive detection technology for various applications. While this technology provides high sensitivity detection of biomarkers, to date, only the time resolved signal was analyzed. Here, we use for the first time both time-resolved and spatial-resolved measurements and show that this combination drastically improves the sensitivity of an MMB-based assay.

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Mar 2023

A ‘golden’alternative for prevention of cisplatin nephrotoxicity in bladder cancer

Yoray Sharon, Menachem Motiei, Chen Tzror-Azankot, Tamar Sadan, Rachela Popovtzer, Eli Rosenbaum

Cisplatin (CP) is the first-line standard of care for bladder cancer. However, a significant percentage of advanced bladder cancer patients are ineligible to receive standard CP treatment, due to the drug’s toxicity, and in particular its nephrotoxicity. These patients currently face suboptimal therapeutic options with lower efficacy. To overcome this limitation, here we designed CP-conjugated gold nanoparticles (GNPs) with specific properties that prevent renal toxicity, and concurrently preserve the therapeutic efficacy of CP. Safety and efficacy of the particles were studied in bladder tumor-bearing mice, using clinically-relevant fractionated or non-fractionated dosing regimens. A non-fractionated high dose of CP-GNP showed long-term intratumoral accumulation, blocked tumor growth, and nullified the lethal effect of CP. Treatment with fractionated lower doses of CP-GNP was also superior to an equivalent treatment with free CP, demonstrating both anti-tumor efficacy and prolonged mouse survival. Moreover, as opposed to free drug, CP-conjugated GNPs did not cause fibrosis or necrosis in kidney. These results indicate that conjugating CP to GNPs can serve as an effective, combined anti-cancer and renoprotective approach, and thus has potential to widen the range of patients eligible for CP-based therapy.

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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 • Journal of Power Sources

Enhanced oxygen reduction and fuel cell performance and durability of ultra-low loading Pt-supported high surface area titanium nitro-carbide

Oran Lori, Alisa Kozhushner, Hilah C Honig, Lior Elbaz

Corrosion resistance, porous structure and high surface area are becoming more and more significant as electrode properties in long-term operation of polymer electrolyte membrane fuel cell. In this work, high surface area, porous titanium-based ceramic compound was synthesized via the facile modified urea glass method (mUGM) and utilized as electrocatalyst support for oxygen resection reaction (ORR) in fuel cells cathodes. The as-prepared compound was found to have surface area and crystallite sizes of the scale of carbon black (CB) with strong dependency on the Ti precursor to urea molar ratio. N–C bonds were found to be involved, as suggested from the X-ray photoelectron spectra, and little to-no residual bulk carbon was found in the samples (X-ray diffraction and Raman spectroscopy). After deposition of Pt metal catalyst, the ceramic-based system demonstrated superior ORR activity and fuel cell …

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Mar 2023 • Current Opinion in Electrochemistry, 101285, 2023

Developing Highly Solvating Electrolyte Solutions for Lithium-Sulfur Batteries

Mengxue He, Kenneth Ikechukwu Ozoemena, Doron Aurbach, Quanquan Pang

The limited polysulfide solubility and the resulted poor kinetics in conventionally preferred electrolyte solutions severely limit the energy density of lithium-sulfur (Li-S) battery under practically lean-electrolyte conditions. Recently, highly solvating electrolyte solutions (HSEs) have been proposed to tackle the challenge because of their high polysulfides solubility. Despite the promised high capacity under lean-electrolyte conditions, the sulfur reaction pathways, the kinetics and the reactivity with lithium remain the major questions regarding this path. This Opinion is positioned to summarize the recent progress on developing HSEs for Li-S battery, aiming to call for attention from the community. We also offer our opinions on whether HSEs are promising and how to improve them for future Li-S battery. We anticipate that the electrolytes strategy that promises high-capacity/high energy Li-S batteries by using HSEs should …

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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 • Molecular Therapy-Nucleic Acids

Multiplex HDR for disease and correction modeling of SCID by CRISPR genome editing in human HSPCs

Ortal Iancu, Daniel Allen, Orli Knop, Yonathan Zehavi, Dor Breier, Adaya Arbiv, Atar Lev, Yu Nee Lee, Katia Beider, Arnon Nagler, Raz Somech, Ayal Hendel

Severe combined immunodeficiency (SCID) is a group of disorders caused by mutations in genes involved in the process of lymphocyte maturation and function. CRISPR-Cas9 gene editing of the patient’s own hematopoietic stem and progenitor cells (HSPCs) ex vivo could provide a therapeutic alternative to allogeneic hematopoietic stem cell transplantation, the current gold standard for treatment of SCID. To eliminate the need for scarce patient samples, we engineered genotypes in healthy donor (HD)-derived CD34+ HSPCs using CRISPR-Cas9/rAAV6 gene-editing, to model both SCID and the therapeutic outcomes of gene-editing therapies for SCID via multiplexed homology-directed repair (HDR). First, we developed a SCID disease model via biallelic knockout of genes critical to the development of lymphocytes; and second, we established a knockin/knockout strategy to develop a proof-of-concept single …

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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 • Nature

RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer

Amina Jbara, Kuan-Ting Lin, Chani Stossel, Zahava Siegfried, Haya Shqerat, Adi Amar-Schwartz, Ela Elyada, Maxim Mogilevsky, Maria Raitses-Gurevich, Jared L Johnson, Tomer M Yaron, Ofek Ovadia, Gun Ho Jang, Miri Danan-Gotthold, Lewis C Cantley, Erez Y Levanon, Steven Gallinger, Adrian R Krainer, Talia Golan, Rotem Karni

Pancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation is correlated with the dissemination of metastases–. Here we analysed RNA splicing data of a large cohort of primary and metastatic PDA tumours to identify differentially spliced events that correlate with PDA progression. De novo motif analysis of these events detected enrichment of motifs with high similarity to the RBFOX2 motif. Overexpression of RBFOX2 in a patient-derived xenograft (PDX) metastatic PDA cell line drastically reduced the metastatic potential of these cells in vitro and in vivo, whereas depletion of RBFOX2 in primary pancreatic tumour cell lines increased the metastatic potential of these cells. These findings support the role of RBFOX2 as a potent metastatic suppressor in …

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Mar 2023 • Advanced Optical Materials 11 (5), 2201475, 2023

Linear and Nonlinear Optical Properties of Well‐Defined and Disordered Plasmonic Systems: A Review

Racheli Ron, Tchiya Zar, Adi Salomon

Disordered metallic nanostructures have features that are not realized in well‐defined nanometallic counterparts, such as broadband light localization and inhomogeneous refraction index at the nanoscale. Disordered metal systems with a networked inner architecture have both particles and voids with subwavelength dimensions which are randomly 3D organized in space. These disordered structures are benefited from high surface area and damage stability, permit guest materials permeability, and can be achieved in large scales employing less costs and expertise. Their abundant nanosize gaps and sharp tips can interact with incident light over a broadband range to generate a rich pattern of hot‐spots and can therefore function as an artificial leaf, for example. Here, the linear and nonlinear optical properties of both well‐defined and disordered plasmonic structures are reviewed with a focus on largescale 3D …

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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 • 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 • 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 • Journal of Biophotonics

Fluorescence attenuated by a thick scattering medium: theory, simulations and experiments

Yitzchak Weber, Hamootal Duadi, Pavitra Sokke Rudraiah, Inbar Yariv, Gilad Yahav, Dror Fixler, Rinat Ankri

Fluorescence‐based imaging has an enormous impact on our understanding of biological systems. However, in vivo fluorescence imaging is greatly influenced by tissue scattering. A better understanding of this dependance can improve the potential of non‐invasive in vivo fluorescence imaging. In this paper we present a diffusion model, based on an existing master‐slave model, of isotropic point sources imbedded in a scattering slab, representing fluorophores within a tissue. The model was compared to Monte Carlo simulations and measurements of a fluorescent slide measured through tissue‐like phantoms with different reduced scattering coefficients (0.5 to 2.5mm‐1) and thicknesses(0.5 to 5mm). Results show a good correlation between our suggested theory, simulations and experiments; while the fluorescence intensity decays as the slab's scattering and thickness increase, the decay rate decreases as the …

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Mar 2023 • arXiv e-prints

Leggett–Garg-like Inequalities from a Correlation Matrix Construction

Dana Ben Porath, Eliahu Cohen

The Leggett-Garg Inequality (LGI) constrains, under certain fundamental assumptions, the correlations between measurements of a quantity Q at different times. Here we analyze the LGI, and propose similar but somewhat more elaborate inequalities, employing a technique that utilizes the mathematical properties of correlation matrices, which was recently proposed in the context of nonlocal correlations. We also find that this technique can be applied to inequalities that combine correlations between different times (as in LGI) and correlations between different locations (as in Bell inequalities). All the proposed bounds include additional correlations compared to the original ones and also lead to a particular form of complementarity. A possible experimental realization and some applications are briefly discussed.

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Feb 2023 • Biomass Conversion and Biorefinery

Biomass-derived Carbon dots and their coated surface as a potential antimicrobial agent

R Blessy Pricilla, Moorthy Maruthapandi, Arulappan Durairaj, Ivo Kuritka, John HT Luong, Aharon Gedanken

Carbon dots (CDs) with an average diameter of 6.3 nm were synthesized from the medicinal seed extract of Syzygium cumini L. using one-pot hydrothermal synthesis. The prepared CDs exhibited excitation-dependent emission characteristics with photoluminescence (PL) emission maxima at an excitation of 340 nm. The CDs at 500 µg/mL displayed antimicrobial activities against four common pathogens. Both Staphylococcus aureus and S. epidermidis were completely eradicated by CDs within 12 h, compared to 24 h for Escherichia coli and Klebsiella pneumonia. The release of various oxygen species (ROS) was postulated to play a critical role in bacterial eradication. The CDs decorated on cotton fabric by ultrasonication also displayed good antibacterial activities against the above bacteria. The finding opens a plausible use of CDs in biomedical textiles with potent antimicrobial properties against both Gram …

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Feb 2023 • ImmunoInformatics

AIRR community curation and standardised representation for immunoglobulin and T cell receptor germline sets

William D Lees, Scott Christley, Ayelet Peres, Justin T Kos, Brian Corrie, Duncan Ralph, Felix Breden, Lindsay G Cowell, Gur Yaari, Martin Corcoran, Gunilla B Karlsson Hedestam, Mats Ohlin, Andrew M Collins, Corey T Watson, Christian E Busse, The AIRR Community

Analysis of an individual's immunoglobulin or T cell receptor gene repertoire can provide important insights into immune function. High-quality analysis of adaptive immune receptor repertoire sequencing data depends upon accurate and relatively complete germline sets, but current sets are known to be incomplete. Established processes for the review and systematic naming of receptor germline genes and alleles require specific evidence and data types, but the discovery landscape is rapidly changing. To exploit the potential of emerging data, and to provide the field with improved state-of-the-art germline sets, an intermediate approach is needed that will allow the rapid publication of consolidated sets derived from these emerging sources. These sets must use a consistent naming scheme and allow refinement and consolidation into genes as new information emerges. Name changes should be minimised, but …

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Feb 2023

CRISPR-Cas9 RAG2 Correction Via Coding Sequence Replacement to Preserve Endogenous Gene Regulation and Locus Structure

Daniel Allen, Orli Knop, Bryan Itkowitz, Ortal Iancu, Katia Beider, Yu Nee Lee, Arnon Nagler, Raz Somech, Ayal Hendel

RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2), a gene intimately involved in the process of lymphocyte maturation and function. ex-vivo manipulation of a patient’s own hematopoietic stem and progenitor cells (HSPCs) using CRISPR-Cas9/rAAV6 gene editing could provide a therapeutic alternative to the only current treatment, allogeneic hematopoietic stem cell transplantation (HSCT). Here we show a first-of-its-kind RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) to preserve the critical endogenous spatiotemporal gene regulation and locus architecture. Expression of the corrective transgene led to successful development into CD3+ TCRαβ+ and CD3+ TCRγδ+ T cells and promoted the establishment of highly diverse TRB and TRG repertoires in an in-vitro T-cell differentiation platform. We believe that a CDS replacement technique to correct tightly regulated genes, like RAG2, while maintaining critical regulatory elements and conserving the locus structure could bring safer gene therapy techniques closer to the clinic.

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Feb 2023 • Angewandte Chemie (International ed. in English)

Peptide Bond Formation in the Protonated Serine Dimer Following Vacuum UV Photon‐Induced Excitation

Ori Licht, Dario Barreiro-Lage, Patrick Rousseau, Alexandre Giuliani, Aleksandar Milosavljevic, Avinoam Isaak, Yitzhak Mastai, Amnon Albeck, Raj Singh, Vy Nguyen, Laurent Nahon, Lara Martinez, Sergio Díaz-Tendero, Yoni Toker

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the eV range. Moreover, the comparison of photon induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by {\it ab initio} molecular dynamics and exploration of several excited state potential energy surfaces, unravelling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.

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