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Dec 2023 • Genome Research

A somatic hypermutation–based machine learning model stratifies individuals with Crohn's disease and controls

Modi Safra, Lael Werner, Pazit Polak, Ayelet Peres, Naomi Salamon, Michael Schvimer, Batia Weiss, Iris Barshack, Dror S Shouval, Gur Yaari

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Dec 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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Dec 2023 • EPL

Variance properties of the microwave absorption spectrum of an ensemble of nitrogen vacancy centers in diamond

RA Chelly, T Chang, I Holzman, T Cohen, J Kantorovitsch, M Stern

This work presents an original method based on the variance properties of the microwave absorption spectrum of an ensemble of nitrogen vacancy centers in diamond. The spectrum is measured optically. A compact and simple device is designed to optimize the photon collection. We conduct a quantitative comparison of the ensemble's optical signal in both the visible and near infrared range. Using the enhanced signal-to-noise ratio achieved through the device geometry we perform real-time DC magnetometry at moderate light and microwave powers. Under these conditions, the amplitude of a DC magnetic field can be extracted from the variance of the microwave absorption spectrum in a fast and reproducible manner, without the burden of complex fitting techniques.

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Dec 2023 • Molecular Reproduction and Development 90 (12), 785-803, 2023

Epigenetic aging of mammalian gametes

Michael Klutstein, Nitzan Gonen

The process of aging refers to physiological changes that occur to an organism as time progresses and involves changes to DNA, proteins, metabolism, cells, and organs. Like the rest of the cells in the body, gametes age, and it is well established that there is a decline in reproductive capabilities in females and males with aging. One of the major pathways known to be involved in aging is epigenetic changes. The epigenome is the multitude of chemical modifications performed on DNA and chromatin that affect the ability of chromatin to be transcribed. In this review, we explore the effects of aging on female and male gametes with a focus on the epigenetic changes that occur in gametes throughout aging. Quality decline in oocytes occurs at a relatively early age. Epigenetic changes constitute an important part of oocyte aging. DNA methylation is reduced with age, along with reduced expression of DNA …

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Dec 2023 • Advanced Materials Technologies

Biolistic Delivery of Photosensitizer‐Loaded Porous Si Carriers for Localized Photodynamic Therapy (Adv. Mater. Technol. 23/2023)

Elina Haimov‐Talmoud, Michal Rosenberg, Sofia Arshavsky‐Graham, Eli Varon, Orit Shefi, Ester Segal

Highly localized photodynamic therapy (PDT) is achieved by biolistic delivery of photosensitizer-loaded porous silicon microparticles directly into solid tumors, as demonstrated by Orit Shefi, Ester Segal, and co-workers in article 2300877. PDT irradiation following the uptake of the released photosensitizer payload induce substantial inhibition of tumor growth in vivo, opening new possibilities for an improved clinical PDT treatment.

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Dec 2023 • ACS omega

Monte Carlo-Simulated Annealing and Machine Learning-Based Funneled Approach for Finding the Global Minimum Structure of Molecular Clusters

Michal Roth, Yoni Toker, Dan T Major

Understanding the physical underpinnings and geometry of molecular clusters is of great importance in many fields, ranging from studying the beginning of the universe to the formation of atmospheric particles. To this end, several approaches have been suggested, yet identifying the most stable cluster geometry (i.e., global potential energy minimum) remains a challenge, especially for highly symmetric clusters. Here, we suggest a new funneled Monte Carlo-based simulated annealing (SA) approach, which includes two key steps: generation of symmetrical clusters and classification of the clusters according to their geometry using machine learning (MCSA-ML). We demonstrate the merits of the MCSA-ML method in comparison to other approaches on several Lennard-Jones (LJ) clusters and four molecular clusters─Ser8(Cl–)2, H+(H2O)6, Ag+(CO2)8, and Bet4Cl–. For the latter of these clusters, the correct …

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Dec 2023 • Journal of Biological Engineering

A streptavidin–biotin system combined with magnetic actuators for remote neuronal guidance

Dafna Rivka Levenberg, Eli Varon, Ganit Indech, Tal Ben Uliel, Lidor Geri, Amos Sharoni, Orit Shefi

The ability to control neuronal mobility and organization is of great importance in developing neuronal interfaces and novel therapeutic approaches. An emerging promising method is the manipulation of neuronal cells from afar via magnetic forces. Nevertheless, using magnetic iron oxide nanoparticles as internal actuators may lead to biotoxicity, adverse influence on intracellular processes, and thus requires prerequisite considerations for therapeutic approaches. Magnetizing the cells via the incorporation of magnetic particles that can be applied extracellularly is advantageous. Herein, we have developed a magnetic system based on streptavidin–biotin interaction to decorate cellular membrane with magnetic elements. In this model, superparamagnetic microparticles, coated with streptavidin, were specifically bound to biotinylated PC12 cells. We demonstrated that cell movement can be directed remotely by the forces produced by pre-designed magnetic fields. First, using time lapse imaging, we analyzed the kinetics of cell migration towards the higher flux zone. Next, to form organized networks of cells we designed and fabricated micro-patterned magnetic devices. The fabricated devices were composed of a variety of ferromagnetic shapes, sputter-deposited onto glass substrates. Cells that were conjugated to the magnetic particles were plated atop the micro-patterned substrates, attracted to the magnetic actuators and became fixed onto the magnetic patterns. In all, our study presents a novel system based on a well-known molecular technology combined with nanotechnology that may well lead to the expansion of implantable magnetic …

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Dec 2023 • NAR Genomics and Bioinformatics

Elevated A-to-I RNA editing in COVID-19 infected individuals

Rona Merdler-Rabinowicz, David Gorelik, Jiwoon Park, Cem Meydan, Jonathan Foox, Miriam Karmon, Hillel S Roth, Roni Cohen-Fultheim, Galit Shohat-Ophir, Eli Eisenberg, Eytan Ruppin, Christopher E Mason, Erez Y Levanon


Dec 2023 • International Journal of Molecular Sciences

Nicotinamide-expanded allogeneic natural killer cells with CD38 deletion, expressing an enhanced CD38 chimeric antigen receptor, target multiple myeloma cells

Avishay Edri, Nimrod Ben-Haim, Astar Hailu, Nurit Brycman, Orit Berhani-Zipori, Julia Rifman, Sherri Cohen, Dima Yackoubov, Michael Rosenberg, Ronit Simantov, Hideshima Teru, Keiji Kurata, Kenneth Carl Anderson, Ayal Hendel, Aviad Pato, Yona Geffen

Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide a rapid and potent immune response, including direct cytotoxicity and mobilization of the immune system, without the need for antigen processing and presentation. NK cells may also be better tolerated than T cell therapy approaches and are susceptible to various gene manipulations. Therefore, NK cells have become the focus of extensive translational research. Gamida Cell’s nicotinamide (NAM) platform for cultured NK cells provides an opportunity to enhance the therapeutic potential of NK cells. CD38 is an ectoenzyme ubiquitously expressed on the surface of various hematologic cells, including multiple myeloma (MM). It has been selected as a lead target for numerous monoclonal therapeutic antibodies against MM. Monoclonal antibodies target CD38, resulting in the lysis of MM plasma cells through various antibody-mediated mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, significantly improving the outcomes of patients with relapsed or refractory MM. However, this therapeutic strategy has inherent limitations, such as the anti-CD38-induced depletion of CD38-expressing NK cells, thus hindering ADCC. We have developed genetically engineered NK cells tailored to treat MM, in which CD38 was knocked-out using CRISPR-Cas9 technology and an enhanced chimeric antigen receptor (CAR) targeting CD38 was introduced using mRNA electroporation. This combined genetic approach allows for an improved cytotoxic activity directed against …

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Dec 2023 • Molecular Therapy-Nucleic Acids 34, 2023

Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi

Alessia Cavazza, Ayal Hendel, Rasmus O Bak, Paula Rio, Marc Güell, Duško Lainšček, Virginia Arechavala-Gomeza, Ling Peng, Fatma Zehra Hapil, Joshua Harvey, Francisco G Ortega, Coral Gonzalez-Martinez, Carsten W Lederer, Kasper Mikkelsen, Giedrius Gasiunas, Nechama Kalter, Manuel AFV Gonçalves, Julie Petersen, Alejandro Garanto, Lluis Montoliu, Marcello Maresca, Stefan E Seemann, Jan Gorodkin, Loubna Mazini, Rosario Sanchez, Juan R Rodriguez-Madoz, Noelia Maldonado-Pérez, Torella Laura, Michael Schmueck-Henneresse, Cristina Maccalli, Julian Grünewald, Gloria Carmona, Neli Kachamakova-Trojanowska, Annarita Miccio, Francisco Martin, Giandomenico Turchiano, Toni Cathomen, Yonglun Luo, Shengdar Q Tsai, Karim Benabdellah

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the "Genome Editing to treat Human Diseases" (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi's primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop …

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Dec 2023 • Journal of Biological Engineering

A streptavidin–biotin system combined with magnetic actuators for remote neuronal guidance

Dafna Rivka Levenberg, Eli Varon, Ganit Indech, Tal Ben Uliel, Lidor Geri, Amos Sharoni, Orit Shefi

The ability to control neuronal mobility and organization is of great importance in developing neuronal interfaces and novel therapeutic approaches. An emerging promising method is the manipulation of neuronal cells from afar via magnetic forces. Nevertheless, using magnetic iron oxide nanoparticles as internal actuators may lead to biotoxicity, adverse influence on intracellular processes, and thus requires prerequisite considerations for therapeutic approaches. Magnetizing the cells via the incorporation of magnetic particles that can be applied extracellularly is advantageous. Herein, we have developed a magnetic system based on streptavidin–biotin interaction to decorate cellular membrane with magnetic elements. In this model, superparamagnetic microparticles, coated with streptavidin, were specifically bound to biotinylated PC12 cells. We demonstrated that cell movement can be directed remotely by the forces produced by pre-designed magnetic fields. First, using time lapse imaging, we analyzed the kinetics of cell migration towards the higher flux zone. Next, to form organized networks of cells we designed and fabricated micro-patterned magnetic devices. The fabricated devices were composed of a variety of ferromagnetic shapes, sputter-deposited onto glass substrates. Cells that were conjugated to the magnetic particles were plated atop the micro-patterned substrates, attracted to the magnetic actuators and became fixed onto the magnetic patterns. In all, our study presents a novel system based on a well-known molecular technology combined with nanotechnology that may well lead to the expansion of implantable magnetic …

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Nov 2023 • Angewandte Chemie

Is “water in salt” electrolytes the ultimate solution? Achieving high stability of organic anodes in diluted electrolyte solutions via a wise anions selection

Amey Nimkar, Khorsed Alam, Gil Bergman, Mikhael D Levi, Dan Thomas Major, Netanel Shpigel, Doron Aurbach

The introduction of the water‐in‐salt (WIS) electrolytes concept to prevent water splitting and widen the electrochemical stability window, has spurred extensive research efforts toward development of improved aqueous batteries. The successful implementation of these electrolyte solutions in many electrochemical systems shifts the focus from diluted to WIS electrolyte solutions. Considering the high costs and the tendency of these nearly saturated solutions to crystallize, this trend can be carefully re‐evaluated. Herein we show that the stability of organic electrodes comprising the active material perylene‐3,4,9,10‐tetracarboxylic dianhydride (PTCDA), is strongly influenced by the solvation character of the anions rather than the concentration of the electrolyte solution. Even though the charging process of PTCDA involves solely insertion of cations (i.e., principal counter‐ions), surprisingly, the dominant factor …

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Nov 2023 • MDPI-Multidisciplinary Digital Publishing Institute, 2023

Acceleration of Biodiesel Production

Indra Neel Pulidindi, Aharon Gedanken

The development of renewable energy sources will help alleviate the twin problems of energy appetite and environmental pollution. Among such renewable sources, biofuels standout. Biodiesel is at the top of the list of biofuels that have the potential to substitute conventional fossil-based transportation fuels. The reprint comprises 11 chapters in total dealing with a variety of feedstock needed for the sustainable production of biodiesel, various catalysts that could be used for the accelerated production of biodiesel, and advances in reactor technology for the demand-based production of biodiesel. Indebtedness is due to various research groups, namely: Fahad Rehman and co-workers from Pakistan, Qatar, and the UK; Tao Lyu and co-workers from the UK, China, and Germany; Sandro L. Barbosa and co-workers from Brazil and the USA; Anita Salic and co-workers from Croatia; Fabrizio Roncaglia and co-workers …

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Nov 2023 • Journal of the American Chemical Society

Near-temperature-independent electron transport well beyond expected quantum tunneling range via bacteriorhodopsin multilayers

Sudipta Bera, Jerry A Fereiro, Shailendra K Saxena, Domenikos Chryssikos, Koushik Majhi, Tatyana Bendikov, Lior Sepunaru, David Ehre, Marc Tornow, Israel Pecht, Ayelet Vilan, Mordechai Sheves, David Cahen

A key conundrum of biomolecular electronics is efficient electron transport (ETp) through solid-state junctions up to 10 nm, often without temperature activation. Such behavior challenges known charge transport mechanisms, especially via nonconjugated molecules such as proteins. Single-step, coherent quantum-mechanical tunneling proposed for ETp across small protein, 2–3 nm wide junctions, but it is problematic for larger proteins. Here we exploit the ability of bacteriorhodopsin (bR), a well-studied, 4–5 nm long membrane protein, to assemble into well-defined single and multiple bilayers, from ∼9 to 60 nm thick, to investigate ETp limits as a function of junction width. To ensure sufficient signal/noise, we use large area (∼10–3 cm2) Au–protein–Si junctions. Photoemission spectra indicate a wide energy separation between electrode Fermi and the nearest protein-energy levels, as expected for a polymer of …

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Nov 2023 • Nature Communications

A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei

K Shanmugha Rajan, Hava Madmoni, Anat Bashan, Masato Taoka, Saurav Aryal, Yuko Nobe, Tirza Doniger, Beathrice Galili Kostin, Amit Blumberg, Smadar Cohen-Chalamish, Schraga Schwartz, Andre Rivalta, Ella Zimmerman, Ron Unger, Toshiaki Isobe, Ada Yonath, Shulamit Michaeli

Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal. A single knock-out of a snoRNA guiding Ψ530 on H69 altered the composition of the 80S monosome. These changes specifically affected the translation of only a subset of proteins. This study correlates a single site Ψ modification with changes in ribosomal protein stoichiometry, supported by a high-resolution cryo-EM structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.

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Nov 2023 • medRxiv

Supplementation with short-chain fatty acids and the prebiotic 2FL improves clinical outcome in PD

Tobias Hegelmaier, Alexander Duscha, Christiane Desel, Sabrina Fuchs, Michal Shapira, Qihao Shan, Gabriele I Stangl, Frank Hirche, Stefan Kempa, Andras Maifeld, Lisa-Marie Würtele, Jana Peplinski, Diana Jauk, Claudia A Dumitru, Ute Obermüller-Jevic, Svein-Olaf Hustvedt, Nina Timmesfeld, Ralf Gold, Antonia Zapf, Ibrahim E Sandalcioglu, Sanaz Mostaghim, Horst Przuntek, Eran Segal, Nissan Yissachar, Aiden Haghikia

BackgroundParkinson’s disease (PD) is associated with dysbiosis, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance. Microbiota-produced short-chain fatty acids promote gut barrier integrity and immune regulation, but their impact on PD pathology remains mostly unknown.ObjectivesTo evaluate supplementation with short-chain fatty acids as an add-on intervention in PD.MethodsIn a randomized double-blind prospective study, 72 PD patients received short-chain fatty acids and/or the prebiotic fiber 2′-fucosyllactose supplementation over 6 months.ResultsWe observed improvement in motor and nonmotor symptoms, in addition to modulation of peripheral immunity and improved mitochondrial respiration in immunocytes. The supplementation had no effect on microbiome diversity or composition. Finally, multiobjective analysis and comprehensive immunophenotyping revealed parameters associated with an optimal response to short-chain fatty acids and/or 2′-fucosyllactose supplementation.ConclusionShort-chain fatty acids ameliorate clinical symptoms in Parkinson’s disease patients and modulate mitochondrial function and peripheral immunity.

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Nov 2023 • ACS Applied Bio Materials

Zirconium-Coated β-Cyclodextrin Nanomaterials for Biofilm Eradication

Akanksha Gupta, John HT Luong, Aharon Gedanken

Under alkaline treatment, zirconyl chloride (ZrOCl2.8H2O) became a zirconia gel and formed a stable complex with beta-cyclodextrin (βCD). This complex was highly active in reactive oxygen species (ROS) formation via H2O2 decomposition. Its surface with numerous hydroxyl groups acts as an ionic sponge to capture the charged reaction intermediates, including superoxide (O2–•) and the hydroxyl radical (•OH). ROS, especially •OH radicals, are harmful to living microorganisms because of their kinetic instability, high oxidation potential, and chemical nonselectivity. Therefore, •OH radicals can engage in fast reactions with virtually any adjacent biomolecule. With H2O2, the complex with cationic and hydrophobic moieties interacted with the anionic bacterial membrane of two Gram-positive (Staphylococcus aureus and S. epidermidis) and two Gram-negative (Escherichia coli and Klebsiella pneumoniae) strains …

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Nov 2023 • ACS Applied Bio Materials

Zirconium-Coated β-Cyclodextrin Nanomaterials for Biofilm Eradication

Akanksha Gupta, John HT Luong, Aharon Gedanken

Under alkaline treatment, zirconyl chloride (ZrOCl2.8H2O) became a zirconia gel and formed a stable complex with beta-cyclodextrin (βCD). This complex was highly active in reactive oxygen species (ROS) formation via H2O2 decomposition. Its surface with numerous hydroxyl groups acts as an ionic sponge to capture the charged reaction intermediates, including superoxide (O2–•) and the hydroxyl radical (•OH). ROS, especially •OH radicals, are harmful to living microorganisms because of their kinetic instability, high oxidation potential, and chemical nonselectivity. Therefore, •OH radicals can engage in fast reactions with virtually any adjacent biomolecule. With H2O2, the complex with cationic and hydrophobic moieties interacted with the anionic bacterial membrane of two Gram-positive (Staphylococcus aureus and S. epidermidis) and two Gram-negative (Escherichia coli and Klebsiella pneumoniae) strains …

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Nov 2023 • Ultrasonics Sonochemistry

Ultrasonic-assisted synthesis of lignin-capped Cu2O nanocomposite with antibiofilm properties

Moorthy Maruthapandi, Akanksha Gupta, Arumugam Saravanan, Gila Jacobi, Ehud Banin, John HT Luong, Aharon Gedanken

Under ultrasonication, cuprous oxide (Cu2O) microparticles (<5 µm) were fragmented into nanoparticles (NPs, ranging from 10 to 30 nm in diameter), and interacted strongly with alkali lignin (Mw= 10 kDa) to form a nanocomposite. The ultrasonic wave generates strong binding interaction between lignin and Cu2O. The L-Cu nanocomposite exhibited synergistic effects with enhanced antibiofilm activities against E. coli, multidrug-resistant (MDR) E. coli, S. aureus (SA), methicillin-resistant SA, and P. aeruginosa (PA). The lignin-Cu2O (L-Cu) nanocomposite also imparted notable eradication of such bacterial biofilms. Experimental evidence unraveled the destruction of bacterial cell walls by L-Cu, which interacted strongly with the bacterial membrane. After exposure to L-Cu, the bacterial cells lost the integrated structural morphology. The estimated MIC for biofilm inhibition for the five tested pathogens was 1 mg/mL L …

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Nov 2023 • MDPI-Multidisciplinary Digital Publishing Institute, 2023

Catalytic Methods for the Synthesis of Carbon Nanodots and Their Applications

Indra Neel Pulidindi, Archana Deokar, Aharon Gedanken

The current endeavor of publishing a reprint on the astounding field of research on carbon dots has its roots in the launch of the Special Issue entitled" Catalytic methods for the synthesis of carbon nanodots and their applications”. Ever since this Special Issue was launched on 29th August 2022, it has attracted great attention from researchers worldwide. Grateful thanks are due to Dr. Nimala Kumar Jangid and coworkers from India; Dr. Syed Hadi Hasan and coworkers from India; Dr. Lerato L Mokoloko and coworkers from South Africa; Dr. Siti Kastom Kamarudin and coworkers from Malaysia; Dr. Selvaraj Roomani and coworkers from India; Dr. Ahmad Umar and coworkers from India, Saudi Arabia and USA; Dr. Ramon Moreno-Tost and coworkers from Spain; Dr. Jae Hong Kim and coworkers from South Korea and Japan; Dr. Yong RokLee and coworkers from India, South Korea and UAE; and Dr. Joydeep Das from …

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Nov 2023 • APL Photonics

Supercontinuum generation by saturated second-order nonlinear interactions

Marc Jankowski, Carsten Langrock, Boris Desiatov, Marko Lončar, MM Fejer

We propose a new approach to supercontinuum generation and carrier-envelope-offset detection based on saturated second-order nonlinear interactions in dispersion-engineered nanowaveguides. The technique developed here broadens the interacting harmonics by forming stable bifurcations of the pulse envelopes due to an interplay between phase-mismatch and pump depletion. We first present an intuitive heuristic model for spectral broadening by second-harmonic generation of femtosecond pulses and show that this model agrees well with experiments. Then, having established strong agreement between theory and experiment, we develop scaling laws that determine the energy required to generate an octave of bandwidth as a function of input pulse duration, device length, and input pulse chirp. These scaling laws suggest that future realization based on this approach could enable supercontinuum …

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