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Oct 2019 • Bioinformatics

Corrigendum to: A new cis-acting regulatory element driving gene expression in the zebrafish pineal gland

Shahar Alon, Eli Eisenberg, Jasmine Jacob-Hirsch, Gideon Rechavi, Gad Vatine, Reiko Toyama, Steven L Coon, David C Klein, Yoav Gothilf

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Oct 2019 • ACS catalysis

Oscillatory active-site motions correlate with kinetic isotope effects in formate dehydrogenase

Philip Pagano, Qi Guo, Chethya Ranasinghe, Evan Schroeder, Kevin Robben, Florian Hase, Hepeng Ye, Kyle Wickersham, Alán Aspuru-Guzik, Dan T Major, Lokesh Gakhar, Amnon Kohen, Christopher M Cheatum

Thermal motions of enzymes have been invoked to explain the temperature dependence of kinetic isotope effects (KIEs) in enzyme-catalyzed hydride transfers. Formate dehydrogenase (FDH) from Candida boidinii exhibits a temperature-independent KIE that becomes temperature-dependent upon mutation of hydrophobic residues in the active site. Ternary complexes of FDH that mimic the transition state structure allow investigation of how these mutations influence active-site dynamics. A combination of X-ray crystallography, two-dimensional infrared (2D IR) spectroscopy, and molecular dynamic simulations characterize the structure and dynamics of the active site. FDH exhibits oscillatory frequency fluctuations on the picosecond timescale, and the amplitude of these fluctuations correlates with the temperature dependence of the KIE. Both the kinetic and dynamic phenomena can be reproduced computationally …

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Oct 2019 • Biomedical optics express

Ratiometric widefield imaging with spectrally balanced detection

Shimon Yudovich, Lior Shani, Asaf Grupi, Omri Bar-Elli, Dan Steinitz, Dan Oron, Shimon Weiss

Ratiometric imaging is an invaluable tool for quantitative microscopy, allowing for robust detection of FRET, anisotropy, and spectral shifts of nano-scale optical probes in response to local physical and chemical variations such as local pH, ion composition, and electric potential. In this paper, we propose and demonstrate a scheme for widefield ratiometric imaging that allows for continuous tuning of the cutoff wavelength between its two spectral channels. This scheme is based on angle-tuning the image splitting dichroic beamsplitter, similar to previous works on tunable interference filters. This configuration allows for ratiometric imaging of spectrally heterogeneous samples, which require spectral tunability of the detection path in order to achieve good spectrally balanced ratiometric detection.

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Oct 2019 • 2019 International Topical Meeting on Microwave Photonics (MWP), 1-4, 2019

An Integrated Discrete-Time Microwave Photonic Filter Using Surface Acoustic Waves in Silicon

Dvir Munk, Moshe Katzman, Mirit Hen, Maayan Priel, Arik Bergman, Avi Zadok

An integrated discrete-time microwave-photonic filter is implemented in standard silicon-on-insulator based on opto-mechanical interactions. Radio-frequency modulation of an incident optical pump is converted into slow-moving surface acoustic waves. The surface waves are delayed by up to 40 ns over 150 microns on-chip. Signals are recovered in the optical domain through photo-elastic modulation of probe light in multiple standard waveguides along the surface acoustic waves path. Devices do not require the suspension of silicon structures, piezo-electric actuation or hybrid material integration. A six-tap filter is demonstrated experimentally, with a central frequency, free spectral range and passbands width of 2.4 GHz, 125 MHz and 20 MHz, respectively. The measured transfer function is in excellent agreement with design. The results establish a new concept for integrated microwave photonics processing in …

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Oct 2019 • JOSA A

Broadband field-of-view expansion using a pair of digital micromirror devices

Daniel Dahan, Ami Yaacobi, Gil Aharonovich, Ephraim Pinsky, Zeev Zalevsky

Broadband field-of-view expansion using computational optics methods is presented. A pair of chirp gratings, implemented by digital micromirror devices, is placed on the optical entrance pupil plane of an optical system. The gratings perform achromatic translations of the image across the camera, and a wide image is reconstructed by a post-processing procedure. Optical design for such a system is proposed, and physical analysis shows the considerations of using these optical elements. All methods are established by simulations and experiments.

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Oct 2019 • The Journal of Physical Chemistry C

Nanoparticle Positioning on Liquid and Polymerized Faceted Droplets

Orlando Marin, Moshe Deutsch, David Zitoun, Eli Sloutskin

Nanoparticle (NP)-decorated emulsion droplets are widely employed in science and technology. Yet, no method for a precise positional control of individual NPs on the droplet’s surface has been hitherto demonstrated, thus restricting the nanotechnological application of such systems. Here, we present such a method based on the surface-freezing effect, which forms a crystalline monolayer at the surface of oil-in-water emulsion droplets, and, upon further cooling, renders the liquid droplets faceted. We demonstrate experimentally that by tuning the temperature (T) below the faceting temperature, Td, the NPs spontaneously self-position at the vertices of the faceted droplets because this reduces the system’s elastic energy. The precise vertex positions of the NPs are revealed by scanning electron microscopy of faceted droplets that were solidified by polymerization at T < Td. The details of the energetics underlying …

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Oct 2019 • Biomedical Optics Express

High-resolution VSDI retinotopic mapping via a DLP-based projection system

Adi Gross, Nadav H Ivzan, Nairouz Farah, Yossi Mandel

High-resolution recording of visual cortex activity is an important tool for vision research. Using a customized digital mirror device (DMD) - based system equipped with retinal imaging, we projected visual stimuli directly on the rat retina and recorded cortical responses by voltage-sensitive dye imaging. We obtained robust cortical responses and generated high-resolution retinotopic maps at an unprecedented retinal resolution of 4.6 degrees in the field of view, while further distinguishing between normal and pathological retinal areas. This system is a useful tool for studying the cortical response to localized retinal stimulation and may shed light on various cortical plasticity processes.

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Oct 2019 • Methods

High-throughput smFRET analysis of freely diffusing nucleic acid molecules and associated proteins

Maya Segal, Antonino Ingargiola, Eitan Lerner, SangYoon Chung, Jonathan A White, Aaron Streets, S Weiss, X Michalet

Single-molecule Förster resonance energy transfer (smFRET) is a powerful technique for nanometer-scale studies of single molecules. Solution-based smFRET, in particular, can be used to study equilibrium intra- and intermolecular conformations, binding/unbinding events and conformational changes under biologically relevant conditions without ensemble averaging. However, single-spot smFRET measurements in solution are slow. Here, we detail a high-throughput smFRET approach that extends the traditional single-spot confocal geometry to a multispot one. The excitation spots are optically conjugated to two custom silicon single photon avalanche diode (SPAD) arrays. Two-color excitation is implemented using a periodic acceptor excitation (PAX), allowing distinguishing between singly- and doubly-labeled molecules. We demonstrate the ability of this setup to rapidly and accurately determine FRET …

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Oct 2019 • Energy Technology

Aqueous Energy Storage Device Based on LiMn2O4 (Spinel) Positive Electrode and Anthraquinone‐Modified Carbon‐Negative Electrode

Ortal Hanna, David Malka, Shalom Luski, Thierry Brousse, Doron Aurbach

This article describes the design and tests of aqueous hybrid energy‐storage devices based on activated carbon‐negative electrode and LiMn2O4 (spinel) positive electrode. For this study, activated carbons from two different sources are selected and are further improved by grafting with electroactive anthraquinone molecules. The electrolyte solution is aqueous 1 m Li2SO4 with pH = 7.5. The performances of balanced hybrid devices are characterized by cyclic voltammetry and galvanostatic measurements. It is possible to charge the hybrid cells up to 1.5 V and cycle them with current densities of 40 mA g−1 (mass of positive electrode). These fully balanced cells can achieve thousands of cycles with capacities up to 75 mAh g−1. Preliminary calculations predict that such devices may reach energy density approaching 35 Wh kg−1 (total mass of active materials in both electrodes). Herein, a model of …

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Oct 2019 • Scientific reports

Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice

Soren Hayrabedyan, Reut Shainer, Zhanna Yekhtin, Lola Weiss, Osnat Almogi-Hazan, Reuven Or, Charles L Farnsworth, Scott Newsome, Krassimira Todorova, Michael J Paidas, Chaya Brodie, Eytan R Barnea, Martin Mueller

An autoimmune response against myelin protein is considered one of the key pathogenic processes that initiates multiple sclerosis (MS). The currently available MS disease modifying therapies have demonstrated to reduce the frequency of inflammatory attacks. However, they appear limited in preventing disease progression and neurodegeneration. Hence, novel therapeutic approaches targeting both inflammation and neuroregeneration are urgently needed. A new pregnancy derived synthetic peptide, synthetic PreImplantation Factor (sPIF), crosses the blood-brain barrier and prevents neuro-inflammation. We report that sPIF reduces paralysis and de-myelination of the brain in a clinically-relevant experimental autoimmune encephalomyelitis mice model. These effects, at least in part, are due to post-translational modifications, which involve cyclic AMP dependent protein kinase (PKA), calcium-dependent protein …

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Oct 2019 • Small

Anti‐VEGF‐Aptamer Modified C‐Dots—A Hybrid Nanocomposite for Topical Treatment of Ocular Vascular Disorders

Asaf Shoval, Amos Markus, Zhixin Zhou, Xia Liu, Rémi Cazelles, Itamar Willner, Yossi Mandel

The vascular endothelial growth factor (VEGF) induces pathological angiogenetic ocular diseases. It is a scientific challenge to develop carriers for the controlled release of inhibitors for VEGF present in the back of the eye domain. Carbon dots (C‐dots) functionalized with the VEGF aptamer are introduced and the hybrid nanoparticles are used for ocular nanomedicine. The C‐dots are applied as effective carriers of the anti‐VEGF aptamer across the cornea, yielding therapeutic levels upon topical administration. The hybrids show no toxicity for both in vitro and in vivo murine animal model, and further enable noninvasive intraocular concentration monitoring through the C‐dots inherent fluorescence. In addition, the hybrid C‐dots effectively inhibit VEGF‐stimulated angiogenesis in choroidal blood vessels. This inhibition is comparable to two commercially available anti‐VEGF drugs, bevacizumab and aflibercept. The …

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Oct 2019 • ChemCatChem

Electrocatalytically Active Silver Organic Framework: Ag (I)‐complex Incorporated in Activated Carbon

shmuel Gonen, Oran Lori, Ohad Fleker, Lior Elbaz

Silver is known as a viable alternative for platinum group metals for the catalysis of the oxygen reduction reaction in alkaline electrolyte. Unlike most other platinum‐group metal‐free catalysts, usually organo‐metallic complexes, silver is commonly used in its metallic form (Ag(0)). Herein, we describe the preparation, characterization, and electrochemical activity of a unique silver‐based catalyst, based on Ag(I) ions coordinated to oxygen groups in an organic ligand (benzene tricarboxylic acid ‐ BTC) which forms a metal organic framework, similar to first‐row transition metal‐based catalysts in metal organic frameworks. When the silver‐based catalyst is incorporated in a porous carbon support, it exhibits high electrocatalytic activity for the oxygen reduction reaction, with a distinct electrochemical behavior, different than metallic silver. In addition, the use of the ionic form of the silver, which is atomically dispersed …

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Oct 2019 • Current opinion in structural biology 58, 26-33, 2019

Copper trafficking in eukaryotic systems: Current knowledge from experimental and computational efforts

Alessandra Magistrato, Matic Pavlin, Zena Qasem, Sharon Ruthstein

Copper plays a vital role in fundamental cellular functions, and its concentration in the cell must be tightly regulated, as dysfunction of copper homeostasis is linked to severe neurological diseases and cancer. This review provides a compendium of current knowledge regarding the mechanism of copper transfer from the blood system to the Golgi apparatus; this mechanism involves the copper transporter hCtr1, the metallochaperone Atox1, and the ATPases ATP7A/B. We discuss key insights regarding the structural and functional properties of the hCtr1-Atox1-ATP7B cycle, obtained from diverse studies relying on distinct yet complementary biophysical, biochemical, and computational methods. We further address the mechanistic aspects of the cycle that continue to remain elusive. These knowledge gaps must be filled in order to be able to harness our understanding of copper transfer to develop therapeutic …

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Oct 2019 • The Journal of clinical and aesthetic dermatology

Topical hyaluronic acid facial cream with new micronized molecule technology effectively penetrates and improves facial skin quality: results from in-vitro, ex-vivo, and in …

R Lubart, I Yariv, D Fixler, A Lipovsky

Background: Topical hyaluronic acid (HA) has shown effectiveness in maintaining skin hydration. Topical creams containing HA are widely available, but their efficacy is limited by their lack of penetration into the skin due to the large molecule size of HA, the result of being formulated into a cream base. Objective: In this three-part study (in vitro, ex vivo, and in vivo), molecule sizes, penetration levels, and antiaging qualities of a topical HA facial cream that was formulated using a new technology that micronizes HA molecules (m-HA) were assessed. Methods and Results: Particle sizes of m-HA were evaluated using electron microscopy, which showed varying sizes, the smallest of which was 100nm in diameter. The antioxidation capabilities of m-HA were measured using electron spin resonance and were found to be higher than original HA. Skin penetration of the m-HA formulation was evaluated via …

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Sep 2019 • Biomedical optics express

Optical tissue probing: human skin hydration detection by speckle patterns analysis

Yarden Tzabari Kelman, Sagie Asraf, Nisan Ozana, Nadav Shabairou, Zeev Zalevsky

An optical approach to determine the hydration level in human skin is presented. The approach is based on temporal tracking of back-reflected secondary speckle patterns generated while illuminating the tested area with a laser and applying periodic vibrations to the surface via a controlled vibration source (CVS). This approach has already been tested successfully for other biomedical parameters such as sensing vital signs, hematology and hemodynamic processes in the body. In this paper we examine and adjust this optical technique with the aim of measuring human skin moisture. We compare the suitability and accuracy of our optical method to the commercially available device for skin moisture measurements, the Corneometer CM 825 (by Courage + Khazaka, Cologne, Germany). Preliminary experiments showing the method's suitability for hydration measurements are presented, may lead to more accurate …

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Sep 2019 • Applied Physics Letters

Silicon photodetector for integrated lithium niobate photonics

Boris Desiatov, Marko Lončar

We demonstrate the integration of an amorphous silicon photodetector with a thin film lithium niobate photonic platform operating in the visible wavelength range. We present the details of the design, fabrication, integration, and experimental characterization of this metal-semiconductor-metal photodetector that features a responsivity of 22 mA/W to 37 mA/W over the wide optical bandwidth spanning in the 635 nm–850 nm wavelength range.

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Sep 2019 • Macromolecules

Nanorheology of Polymer Solutions: A Scaling Theory

Yitzhak Rabin, Alexander Y Grosberg

The current theory of viscoelasticity of polymer fluids deals with their response to time-dependent macroscopic perturbations on arbitrary time scales. We use scaling methods to calculate the elastic and dissipative moduli G′ and G″ on length scales that range between monomer size and macroscopic dimensions for several important models of polymer solutions. We find that while both moduli decrease rapidly with decreasing length scale, G′ is more strongly suppressed than G″ at large wave numbers. Possible experimental tests of our predictions are discussed.

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Sep 2019 • Nature communications

Surface acoustic wave photonic devices in silicon on insulator

Dvir Munk, Moshe Katzman, Mirit Hen, Maayan Priel, Moshe Feldberg, Tali Sharabani, Shahar Levy, Arik Bergman, Avi Zadok

Opto-mechanical interactions in planar photonic integrated circuits draw great interest in basic research and applications. However, opto-mechanics is practically absent in the most technologically significant photonics platform: silicon on insulator. Previous demonstrations required the under-etching and suspension of silicon structures. Here we present surface acoustic wave-photonic devices in silicon on insulator, up to 8 GHz frequency. Surface waves are launched through absorption of modulated pump light in metallic gratings and thermo-elastic expansion. The surface waves are detected through photo-elastic modulation of an optical probe in standard race-track resonators. Devices do not involve piezo-electric actuation, suspension of waveguides or hybrid material integration. Wavelength conversion of incident microwave signals and acoustic true time delays up to 40 ns are demonstrated on-chip. Lastly …

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Sep 2019 • Biophysical journal 117 (5), 795-809, 2019

Calibrating evanescent-wave penetration depths for biological TIRF microscopy

Martin Oheim, Adi Salomon, Adam Weissman, Maia Brunstein, Ute Becherer

Roughly half of a cell’s proteins are located at or near the plasma membrane. In this restricted space, the cell senses its environment, signals to its neighbors, and exchanges cargo through exo- and endocytotic mechanisms. Ligands bind to receptors, ions flow across channel pores, and transmitters and metabolites are transported against concentration gradients. Receptors, ion channels, pumps, and transporters are the molecular substrates of these biological processes, and they constitute important targets for drug discovery. Total internal reflection fluorescence (TIRF) microscopy suppresses the background from the cell’s deeper layers and provides contrast for selectively imaging dynamic processes near the basal membrane of live cells. The optical sectioning of TIRF is based on the excitation confinement of the evanescent wave generated at the glass/cell interface. How deep the excitation light actually …

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Sep 2019 • Ultrasonics sonochemistry

Selective production of furfural from the dehydration of xylose using Zn doped CuO catalyst

Rahul Kumar Mishra, Vijay Bhooshan Kumar, Amudavalli Victor, Indra Neel Pulidindi, Aharon Gedanken

Furfural is a versatile biomass-derived platform compound used for the synthesis of several strategic chemicals. The sonochemically synthesized Zn doped CuO nanoparticles (NPs) were used for the production of furfural. The catalytic activity of the Zn doped CuO NPs was examined, as a model, during the dehydration reaction of xylose to furfural. In addition to that, we have also compared the catalytic activity of the Zn doped CuO NP with ZnO NPs, ZnO bulk, CuO NPs, CuO bulk, etc. This nanoscale catalyst (Zn doped CuO NP) has a large surface area, which enhances its catalytic activity and enables it to completely convert the xylose to furfural at 150 °C within 12 h without any trace of by-products, as confirmed by HPLC, 13C NMR and 1H NMR. HPLC analysis demonstrated that the yield of furfural is up to 86 mol %, compared to the 45 mol % obtained with ZnO NPs, ZnO bulk, CuO NPs, CuO bulk, etc. as …

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Sep 2019 • Nature communications

Quantification of porosity in extensively nanoporous thin films in contact with gases and liquids

Netanel Shpigel, Sergey Sigalov, Fyodor Malchik, Mikhael D Levi, Olga Girshevitz, Rafail L Khalfin, Doron Aurbach

Nanoporous layers are widely spread in nature and among artificial devices. However, complex characterization of extensively nanoporous thin films showing porosity-dependent softening lacks consistency and reliability when using different analytical techniques. We introduce herein, a facile and precise method of such complex characterization by multi-harmonic QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring) measurements performed both in the air and liquids (Au-Zn alloy was used as a typical example). The porosity values determined by QCM-D in air and different liquids are entirely consistent with that obtained from parallel RBS (Rutherford Backscattering Spectroscopy) and GISAXS (Grazing-Incidence Small-Angle Scattering) characterizations. This ensures precise quantification of the nanolayer porosity simultaneously with tracking their viscoelastic properties in liquids, significantly …

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