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Mar 2022 • Proc. of SPIE Vol

Identification of inhibitors for the S1-ACE2 interaction of the SARS-CoV-2 using magnetically modulated biosensors

Shira Roth, Amos Danielli, Michael Margulis

The outbreak of the coronavirus disease emphasized the need for fast and sensitive inhibitor screening tools for the identification of new drug candidates. In SARS-CoV-2, one of the initial steps in the infection cycle is the adherence of the receptor-binding domain (RBD) of the spike protein 1 (S1) to the host cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, inhibition of S1-ACE2 interaction may block the entry of the virus to the host cell, and thus may limit the spread of the virus in the body. We demonstrate a rapid and quantitative method for the detection and classification of different types of molecules as inhibitors or non-inhibitors of the S1-ACE2 interaction using magnetically modulated biosensors (MMB). In the MMB-based assay, magnetic beads are attached to the S1 protein and the ACE2 receptor is fluorescently labeled. Thus, only when the proteins interact, the fluorescent …

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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 • Acta Biomaterialia

Molecular differences in collagen organization and in organic-inorganic interfacial structure of bones with and without osteocytes

Raju Nanda, Shani Hazan, Katrein Sauer, Victoria Aladin, Keren Keinan-Adamsky, Björn Corzilius, Ron Shahar, Paul Zaslansky, Gil Goobes

Bone is a fascinating biomaterial comprised mostly of type-I collagen fibers as an organic phase, apatite as an inorganic phase, with water molecules residing at the interfaces between these phases. They are hierarchically organized with minor constituents such as non-collagenous proteins, citrate ions and glycosaminoglycans into a composite structure that is mechanically durable yet contains enough porosity to accommodate cells and blood vessels. The nanometer scale organization of the collagen fibrous structure and the mineral constituents in bone were recently extensively scrutinized. However, molecular details at the lowest hierarchical level still need to be unraveled to better understand the exact atomic-level arrangement of all these important components in the context of the integral structure of the bone. In this report, we unfold some of the molecular characteristics differentiating between two load …

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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 • ChemSusChem 15 (8), e202200027, 2022

What is Next in Anion‐Exchange Membrane Water Electrolyzers? Bottlenecks, Benefits, and Future

Carlo Santoro, Alessandro Lavacchi, Piercarlo Mustarelli, Vito Di Noto, Lior Elbaz, Dario Dekel, Frederic Jaouen

As highlighted by the recent roadmaps from the European Union and the United States, water electrolysis is the most valuable high‐intensity technology for producing green hydrogen. Currently, two commercial low‐temperature water electrolyzer technologies exist ‐ alkaline water electrolyzer (A‐WE) and proton exchange membrane water electrolyzer (PEM‐WE). However, both have major drawbacks. A‐WE shows low productivity and efficiency, while PEM‐WE uses a significant amount of critical raw materials. Lately, the use of anion‐exchange membrane electrolyzers (AEM‐WE) has been proposed to overcome the limitations of the current commercial systems. AEM‐WE could become the cornerstone to achieve an intense, safe and resilient green hydrogen production to fulfill the hydrogen targets to achieve the 2050 decarbonization goals. Here we discuss the status of AEM‐WE development, with a focus on …

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Feb 2022 • Measurement

Diamond protection for reusable ZnO coated fiber-optic measurement head in optoelectrochemical investigation of bisphenol A

Małgorzata Szczerska, Monika Kosowska, Paulina Listewnik, Michał Rycewicz, Mikhael Bechelany, Yafit Fleger, Dror Fixler, Paweł Jakóbczyk

Due to the global problem with plastic contaminating the environment, with bisphenol A (BPA) being one of the highest demand, effective monitoring and purification of the pollutants are required. The electrochemical methods constitute a good solution but, due to polymerization of electrochemical oxidation bisphenol A products and their adsorption to the surfaces, measurement head elements are clogged by the formed film. In this research, we propose a nanocrystalline diamond sheet protection for securing elements in direct contact with bisphenol A during electrochemical processes. The solution was presented on the example of a zinc oxide (ZnO) coating deposited on a fiber-optic end-face by Atomic Layer Deposition. Series of optical and electrochemical measurements were performed in a dedicated hybrid setup. The results show that ZnO can be modified during the electrochemistry leading to the drastic …

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Feb 2022 • Optics Express

Analysis of thin layers using surface acoustic wave-photonic devices in silicon-on-insulator

Mirit Hen, Leroy Dokhanian, Etai Grunwald, Matan Slook, Moshe Katzman, Maayan Priel, Olga Girshevitz, Avi Zadok

The analysis of thin layers deposited on various substrates is widely employed in thickness monitoring, materials research and development and quality control. Measurements are often performed based on changes to acoustic resonance frequencies of quartz micro-balance devices. The technique is extremely sensitive, but it is restricted to hundreds of MHz frequencies and requires electrical connectivity. In this work we propose and demonstrate the analysis of elastic properties of thin layers deposited on surface acoustic wave-photonic devices in standard silicon-on-insulator. The devices operate at 2.4 GHz frequency, and their interfaces are fiber-optic. The radio-frequency transfer functions of the devices are modified by sub-percent level changes to the group velocity of surface acoustic waves following deposition of layers. Layers of aluminum oxide and germanium sulfide of thickness between 10-80 nm are characterized. The analysis provides estimates for Young’s modulus of the layers.

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Feb 2022 • Biophysical Journal

A novel single molecule fluorescence quenching technique for measuring distances below 3 nm

Benjamin Ambrose, Victoria E Hill, Robert A Shaw, Tristan Johnston-Wood, Matthew Willmott, Callum Johnston, Rebecca Mächtel, Thorben Cordes, Eitan Lerner, JG Hill, Shimon Weiss, Timothy D Craggs

Single-molecule FRET (smFRET) is a powerful biophysical tool for measuring intramolecular distances in biomolecules, however FRET is only effective over a 3-10nm scale. In this work we advance a quenching based method which uses Cy3B and Atto647N, a common dye pair used for smFRET. The quenching effect arising from this dye pair is sensitive to distance changes below 3nm, which is significantly lower than its R0 of 6.2 nm. It has previously been used to measure binary on/off transitions, such as local DNA melting in polymerase complexes. However, by using a series of DNAs labelled at various positions we have shown that we can quantitatively distinguish between slight changes in labelling separation. This quenching method is sufficiently sensitive to distinguish between DNAs labelled with dyes 1bp 3′ of each other from those labelled 5′ of each other. Additionally, this effect has been validated …

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Feb 2022 • Photonics

Signal-to-Noise Ratio Improvement for Multiple-Pinhole Imaging Using Supervised Encoder–Decoder Convolutional Neural Network Architecture

Eliezer Danan, Nadav Shabairou, Yossef Danan, Zeev Zalevsky

Digital image devices have been widely applied in many fields, such as individual recognition and remote sensing. The captured image is a degraded image from the latent observation, where the degradation processing is affected by some factors, such as lighting and noise corruption. Specifically, noise is generated in the processing of transmission and compression from the unknown latent observation. Thus, it is essential to use image denoising techniques to remove noise and recover the latent observation from the given degraded image. In this research, a supervised encoder–decoder convolution neural network was used to fix image distortion stemming from the limited accuracy of inverse filter methods (Wiener filter, Lucy–Richardson deconvolution, etc.). Particularly, we will correct image degradation that mainly stems from duplications arising from multiple-pinhole array imaging.

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Feb 2022 • Optics Express

Classification of fluorescent anisotropy decay based on the distance approach in the frequency domain

Gilad Yahav, Yitzchak Weber, Hamootal Duadi, Shweta Pawar, Dror Fixler

Frequency domain Analysis of FI and FA decays and S2. Mathematical formulation of FI and FA decays

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Feb 2022 • Journal of Magnetic Resonance

Shimon Vega in the eyes of his students and postdocs

A Goldbourt, G Goobes, Y Hovav, I Kaminker, V Ladizhansky, M Leskes, PK Madhu, F Mentnik-Vigier, S Pizzanelli, I Sack, D Shimon, J Sunderasan, E Vinogradov

Professor Shimon Vega (1943–2021) of the Weizmann Institute of Science passed away on the 16 th of November. Shimon Vega established theoretical frameworks to develop and explain solid-state nuclear magnetic resonance (NMR) and dynamic nuclear polarization (DNP) techniques and methodologies. His departure left a profound mark on his many students, postdocs, and colleagues. Shortly after his passing, we all assembled spontaneously for an international online meeting to share our reflections and memories of our experiences in Shimon’s lab and how they affected us deeply during that period of time and throughout our scientific careers. These thoughts and feelings were put here into writing.

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Feb 2022 • Biophysical Journal

Single molecule activity assay for SARS-CoV-2 RNA dependent RNA polymerase

SangYoon Chung, Yazan Alhadid, Maya Segal, Jookyung Lee, Sergei Borukhov, Shimon Weiss

Tuesday, February 22, 2022 359a and replication processes. Due to its importance, RdRp is one of the main targets for therapeutic approaches. We developed an in-vitro, single-molecule based assay to detect the polymerization activity of the RdRp complex. Using this assay, we optimized the activity of the minimal SARS-CoV-2 RdRp (composed of nsp12, nsp7, and nsp8) by testing various conditions such as different concentrations of salt, molecular crowding agents, and divalent metal ions. The broad compatibility of our activity assay will enable the study of SARS-CoV-2 transcription and replication mechanisms and will be useful in the development of antiviral agents that inhibit the COVID-19 RdRp and potentially many other viral RdRps.

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Feb 2022 • Applied Surface Science

Energy hot spots distribution on groove surface, elucidated by hybrid optical model in illuminated SOI photo-polarized-activated modulator

David Glukhov, Avihu Zechariah Levi, Zeev Zalevsky, Avi Karsenty

A polarizer transistor sharing a groove filtering aperture was developed. In the device, entitled Silicon-On-Insulator Photo-Polarized Activated Modulator (SOIP2AM), one could think that the larger the V-groove, the higher is the absorbed illumination, and consequently the higher is the amount of new generated pairs of electrons-holes inside the device. In fact, the higher the illumination, the higher the destructive interference points inside the V-groove. Establishing a strong correlation between electrical and optical phenomena, two physical assumptions are presented. The first one is that observed “hot spots” (i.e. intense electrical field areas), are in fact the mirror of optical constructive interferences near the walls of the V-groove. The second assumption is that the closer the hot spots near the wall, the higher the generation of pairs of electrons-holes, since more absorbed photons. A new method, based on analytical …

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Feb 2022 • Biophysical Journal

Controlled membrane interactions by lipid coated quantum dots

Lion Morgenstein, Merav Tsubary, Ayelet Atkins, Asaf Grupi, Shimon Weiss

Quantum Dots (QDs) are being employed in a wide range of biological application due to their superior fluorescence characteristics. Biocompatibility of QDs is usually achieved by exchange of as-synthesized surface ligands with ligands that impart the particle with water solubility properties. An alternative approach for surface functionalization is ligand adsorption. This approach is based on weak interactions between the alkane chains of the as-synthesized surface ligands and a hydrophobic element of an adsorbed ligand with a functional head group/s. There are several advantages for this approach.(i) The photophysical properties stay intact and (ii) the weak association allows for potential adaptive re-distribution of the ligands in response to environment changes. Membrane targeting introduces another layer of complexity and requires precise control of QD’surface properties to control the mode of interaction …

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Feb 2022 • Physical Review E

Generalized virial equation for nonlinear multiplicative Langevin dynamics: Application to laser-cooled atoms

Gianmaria Falasco, Eli Barkai, Marco Baiesi

The virial theorem, and the equipartition theorem in the case of quadratic degrees of freedom, are handy constraints on the statistics of equilibrium systems. Their violation is instrumental in determining how far from equilibrium a driven system might be. We extend the virial theorem to nonequilibrium conditions for Langevin dynamics with nonlinear friction and multiplicative noise. In particular, we generalize it for confined laser-cooled atoms in the semiclassical regime. The resulting relation between the lowest moments of the atom position and velocity allows to measure in experiments how dissipative the cooling mechanism is. Moreover, its violation can reveal the departure from a strictly harmonic confinement or from the semiclassical regime.

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Feb 2022 • arXiv preprint arXiv:2202.00274

Infinite ergodic theory for three heterogeneous stochastic models with application to subrecoil laser cooling

Takuma Akimoto, Eli Barkai, Günter Radons

We compare ergodic properties of the kinetic energy for three stochastic models of subrecoil-laser-cooled gases. One model is based on a heterogeneous random walk (HRW), another is an HRW with long-range jumps (the exponential model), and the other is a mean-field-like approximation of the exponential model (the deterministic model). All the models show an accumulation of the momentum at zero in the long-time limit, and a formal steady state cannot be normalized, i.e., there exists an infinite invariant density. We obtain the exact form of the infinite invariant density and the scaling function for the exponential and deterministic models and devise a useful approximation for the momentum distribution in the HRW model. While the models are kinetically non-identical, it is natural to wonder whether their ergodic properties share common traits, given that they are all described by an infinite invariant density. We show that the answer to this question depends on the type of observable under study. If the observable is integrable, the ergodic properties such as the statistical behavior of the time averages are universal as they are described by the Darling-Kac theorem. In contrast, for non-integrable observables, the models in general exhibit non-identical statistical laws. This implies that focusing on non-integrable observables, we discover non-universal features of the cooling process, that hopefully can lead to a better understanding of the particular model most suitable for a statistical description of the process. This result is expected to hold true for many other systems, beyond laser cooling.

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Feb 2022 • Cancer Research

Abstract PD6-03: Spatio-molecular dissection of the breast cancer metastatic microenvironment

Daniel L Abravanel, Johanna Klughammer, Timothy Blosser, Yury Goltsev, Sizun Jiang, Yunjao Bai, Evan Murray, Shahar Alon, Yi Cui, Daniel R Goodwin, Anubhav Sinha, Ofir Cohen, Michal Slyper, Orr Ashenberg, Danielle Dionne, Judit Jané-Valbuena, Caroline BM Porter, Asa Segerstolpe, Julia Waldman, Sébastien Vigneau, Karla Helvie, Allison Frangieh, Laura DelloStritto, Miraj Patel, Jingyi We, Kathleen Pfaff, Nicole Cullen, Ana Lako, Madison Turner, Isaac Wakiro, Sara Napolitano, Abhay Kanodia, Rebecca Ortiz, Colin MacKichan, Stephanie Inga, Judy Chen, Aaron R Thorner, Asaf Rotem, Scott Rodig, Fei Chen, Edward S Boyden, Garry P Nolan, Xiaowei Zhuang, Orit Rozenblatt-Rosen, Bruce E Johnson, Aviv Regev, Nikhil Wagle

Metastatic breast cancer (MBC) remains incurable due to inevitable development of therapeutic resistance. Although tumor cell intrinsic mechanisms of resistance in MBC are beginning to be elucidated by bulk sequencing studies, the roles of the tumor microenvironment and intratumor heterogeneity in therapeutic resistance remain underexplored due to both technological barriers and limited availability of samples. To comprehensively capture these characteristics we have adapted a research biopsy protocol to collect tissue for an array of single-cell and spatio-molecular assays whose performance we have optimized for MBC, including single-cell and single-nucleus RNA sequencing, Slide-Seq, Multiplexed Error-Robust FISH (MERFISH), Expansion Sequencing (ExSEQ), Co-detection by Indexing (CODEX) and Multiplexed Ion Beam Imaging (MIBI). To date, we have successfully performed single-cell or single …

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Feb 2022 • arXiv preprint arXiv:2202.03640

Special purpose quantum graphs for guaranteed and fast search times

Quancheng Liu, David A Kessler, Eli Barkai

We design monitored quantum walks with the aim of optimizing state transfer and target search. We show how to construct walks with the property that all the eigenvalues of the non-Hermitian survival operator, describing the mixed effect of unitary dynamics and the back-action of measurement, coalesce to zero, corresponding to an exceptional point whose degree is the size of the Hilbert space. Generally, this search is guaranteed to succeed in a bounded time for any initial condition. It also performs better than the classical random walk search or quantum search on typical graphs. For example, a crawler can be designed such that, starting on a node of the graph, the walker is detected on any of the nodes with probability one at predetermined times. It also allows perfect quantum state transfer from one node of the system to any other, with or without monitoring. Interestingly, this crawler is described as a massless Dirac quasi-particle.

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Feb 2022 • Global Change Biology

Urbanization comprehensively impairs biological rhythms in coral holobionts

Yaeli Rosenberg, Noa Simon Blecher, Maya Lalzar, Ruth Yam, Aldo Shemesh, Shahar Alon, Gabriela Perna, Anny Cárdenas, Christian R Voolstra, David J Miller, Oren Levy

Coral reefs are in global decline due to climate change and anthropogenic influences (Hughes et al., 2013). Near coastal cities or other densely populated areas, coral reefs face a range of additional challenges. While considerable progress has been made in understanding coral responses to acute individual stressors (Dominoni et al., 2020), the impacts of chronic exposure to varying combinations of sensory pollutants are largely unknown. To investigate the impacts of urban proximity on corals, we conducted a year‐long in‐natura study ‐ incorporating sampling at diel, monthly, and seasonal time points – in which we compared corals from an Urban area to corals from a proximal Non‐Urban area. Here we reveal that despite appearing relatively healthy, natural biorhythms and environmental sensory systems were extensively disturbed in corals from the Urban environment. Transcriptomic data indicated poor …

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Feb 2022 • Scientific Reports

Author Correction: Picosecond pulsed laser illumination: an ultimate solution for photonic versus thermal processes’ contest in SOI photo-activated modulator

David Glukhov, Zeev Zalevsky, Avi Karsenty

$$\frac {{\partial}^{2}\phi}{\partial {x}^{2}}=-\frac {\partial E}{\partial x}=-\frac {\rho}{\epsilon}\Rightarrow\phi (x)-\phi (0)=-\underset {0}{\overset {x}{\int}} Edx=-\frac {1}{\epsilon}\underset {0}{\overset {x}{\int}}\underset {0}{\overset {{x}^{{\prime}}}{\int}}\rho d {x}^{{\prime}} d {x}^{{\prime}} $$

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Feb 2022 • Physical Review Applied

Visualizing Current in Superconducting Networks

X Wang, M Laav, I Volotsenko, A Frydman, B Kalisky

We present an experimental study of local magnetic imaging in order to visualize the current flow in superconducting networks. We track the evolution of the spatial distribution of the current flow as the network is driven from fully superconducting to fully normal phases. Our results highlight the factors that contribute to the disordered flow in superconducting networks during their collapse, and demonstrate that the current is never uniformly distributed in the network. These results can assist the design and development of circuits based on superconductors and Josephson junctions.

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