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Dec 2022 • International Journal of Molecular Sciences

CT and MRI Imaging of Theranostic Bimodal Fe3O4@Au NanoParticles in Tumor Bearing Mice

Alexey A Lipengolts, Yulia A Finogenova, Vsevolod A Skribitsky, Kristina E Shpakova, Adi Anaki, Menachem Motiei, Alevtina S Semkina, Maxim A Abakumov, Anna V Smirnova, Elena Y Grigorieva, Rachela Popovtzer

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe3O4 core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe3O4@Au theranostic nanoparticles. Core/shell Fe3O4@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe3O4@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe3O4@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.

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Dec 2022 • International Journal of Molecular Sciences

Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor

Tamar Azrad-Leibovich, Alon Zahavi, Moran Friedman Gohas, Myles Brookman, Orit Barinfeld, Orkun Muhsinoglu, Shalom Michowiz, Dror Fixler, Nitza Goldenberg-Cohen

In this study, we characterized diabetic retinopathy in two mouse models and the response to anti-vascular endothelial growth factor (VEGF) injection. The study was conducted in 58 transgenic, non-obese diabetic (NOD) mice with spontaneous type 1 diabetes (n = 30, DMT1-NOD) or chemically induced (n = 28, streptozotocin, STZ-NOD) type 1 diabetes and 20 transgenic db/db mice with type 2 diabetes (DMT2-db/db); 30 NOD and 8 wild-type mice served as controls. Mice were examined at 21 days for vasculopathy, retinal thickness, and expression of genes involved in oxidative stress, angiogenesis, gliosis, and diabetes. The right eye was histologically examined one week after injection of bevacizumab, ranibizumab, saline, or no treatment. Flat mounts revealed microaneurysms and one apparent area of tufts of neovascularization in the diabetic retina. Immunostaining revealed activation of Müller glia and prominent Müller cells. Mean retinal thickness was greater in diabetic mice. RAGE increased and GFAP decreased in DMT1-NOD mice; GFAP and SOX-9 mildly increased in db/db mice. Anti-VEGF treatment led to reduced retinal thickness. Retinas showed vasculopathy and edema in DMT1-NOD and DMT2-db/db mice and activation of Müller glia in DMT1-NOD mice, with some response to anti-VEGF treatment. Given the similarity of diabetic retinopathy in mice and humans, comparisons of type 1 and type 2 diabetic mouse models may assist in the development of new treatment modalities.

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Dec 2022 • Optical Materials Express

Enhanced throughput and clean laser drilling with a sacrificial polymer layer

John Linden, Ariel Hoch, Asaf Levy, Igor Sakaev, Gil Bernstein Toker, Ofer Fogel, Manuela Hod, Zeev Zalevsky

Laser micromachining is the chosen method for vertical interconnect access point (VIA) formation in flex PCB layers. Even so, this method suffers from several inherent physical issues as a result of the intense localized heating causing strong Marangoni convection and the buildup of recast along the VIA upper crater walls while also scattered particle debris and oxidation of copper across the surface. The mitigation of the height and radius of this recast layer is critical for the following build-up process and device functionality and reliability. This is currently a major technology inhibitor to the adoption of flex PCBs for high-power electronics. In this study, we present experimental results showing the use of engineered sacrificial layers that coat the surface of the flex PCB substrate during the laser micromachining process. Optimization of this engineered sacrificial layer resulted in a major improvement in recast quality and debris control as well as reducing the oxide formation while increasing the laser drilling efficiency, attributable to increased surface pressure on the substrate. In this paper, we describe the methods and materials used in the development of sacrificial layers and show the positive impact it achieves on improving and modifying the plasma characteristics throughout the overall laser drilling process.

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Dec 2022 • International Journal of Molecular Sciences

Supermagnetic Human Serum Albumin (HSA) Nanoparticles and PLGA-Based Doxorubicin Nanoformulation: A Duet for Selective Nanotherapy

Julia Malinovskaya, Rawan Salami, Marat Valikhov, Veronika Vadekhina, Aleksey Semyonkin, Alevtina Semkina, Maxim Abakumov, Yifat Harel, Esthy Levy, Tzuriel Levin, Rachel Persky, Vladimir Chekhonin, Jean-Paul Lellouche, Pavel Melnikov, Svetlana Gelperina

Predicting the ability of nanoparticles (NP) to access the tumor is key to the success of chemotherapy using nanotherapeutics. In the present study, the ability of the dual NP-based theranostic system to accumulate in the tumor was evaluated in vivo using intravital microscopy (IVM) and MRI. The system consisted of model therapeutic doxorubicin-loaded poly(lactide-co-glycolide) NP (Dox-PLGA NP) and novel hybrid Ce3/4+-doped maghemite NP encapsulated within the HSA matrix (hMNP) as a supermagnetic MRI contrasting agent. Both NP types had similar sizes of ~100 nm and negative surface potentials. The level of the hMNP and PLGA NP co-distribution in the same regions of interest (ROI, ~2500 µm2) was assessed by IVM in mice bearing the 4T1-mScarlet murine mammary carcinoma at different intervals between the NP injections. In all cases, both NP types penetrated into the same tumoral/peritumoral regions by neutrophil-assisted extravasation through vascular micro- and macroleakages. The maximum tumor contrasting in MRI scans was obtained 5 h after hMNP injection/1 h after PLGA NP injection; the co-distribution level at this time reached 78%. Together with high contrasting properties of the hMNP, these data indicate that the hMNP and PLGA NPs are suitable theranostic companions. Thus, analysis of the co-distribution level appears to be a useful tool for evaluation of the dual nanoparticle theranostics, whereas assessment of the leakage areas helps to reveal the tumors potentially responsive to nanotherapeutics.

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Dec 2022 • arXiv preprint arXiv:2212.04350

Secure communication using low dimensional topological elements

Manuel F Ferrer-Garcia, Avishy Carmi, Alessio D'Errico, Hugo Larocque, Eliahu Cohen, Ebrahim Karimi

Low-dimensional topological objects, such as knots and braids, have become prevalent in multiple areas of physics, such as fluid dynamics, optics, and quantum information processing. Such objects also now play a role in cryptography, where a framed knot can store encoded information using its braid representation for communications purposes. The greater resilience of low-dimensional topological elements under deformations allows them to be employed as a reliable framework for information exchange. Here, we introduce a challenge-response protocol as an application of this construction for authentication. We provide illustrative examples of both procedures showing how framed links and braids may help to enhance secure communication.

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Dec 2022 • Authorea Preprints, 2022

Rn and CO2 in Depth, as a Proxy for Pre-Seismic Activity

Hovav Zafrir, Elad Levintal, Uri Malik, Noam Weisbrod, Yochai Ben Horin, Zeev Zalevsky Zalevsky, Nimrod Inbar

Rn and CO2 in-depth, as a proxy for pre-seismic activity Hovav Zafrir1,4, Uri Malik1, Elad Levintal2, Noam Weisbrod2, Yochai Ben Horin3, Zeev Zalevsky4, Nimrod Inbar5 1Geological Survey of Israel, 32 Yesha'ayahu Leibowitz, Jerusalem 9371234, Israel, 2The Zuckerberg Institute for Water Research, Ben-Gurion University, 8499000 Sede Boqer, Israel, 3Soreq Nuclear Research Center, Yavne 81800, Israel, 4Faculty of Engineering, Bar Ilan University, Ramat-Gan 52900, Israel, 5Ariel University, Ariel 40700, Israel. (First author e-mail: hzafrir@gmail.com; zafrir@gsi.gov.il). Abstract The method of long-term monitoring of subsurface gases in shallow to deep boreholes assumes that the climatic influence on geo-physicochemical parameters is limited since its energy decreases with the increase in the thickness of the geological cover. Hence, the monitoring of radon (Rn), CO2 and other constituents above and …

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Dec 2022 • Journal of Colloid and Interface Science

Strong coupling between an inverse bowtie Nano-Antenna and a J-aggregate

Adam Weissman, Maxim Shukharev, Adi Salomon

We demonstrate strong coupling between a single or few J-aggregates and an inverse bowtie plasmonic structure, when the J-aggregate is located at a specific axial distance from the metallic surface. Three hybrid modes are clearly observed, witnessing a strong interaction, with a Rabi splitting of up to 290 meV, the precise value of which significantly depends on the orientation of the J-aggregate with respect to the symmetry axis of the plasmonic structure. We repeated our experiments with a set of triangular hole arrays, showing consistent formation of three or more hybrid modes, in good agreement with numerical simulations.

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Dec 2022 • European Heart Journal-Digital Health

A novel contact-free atrial fibrillation monitor: a pilot study

Ben Sadeh, Ilan Merdler, Sapir Sadon, Lior Lupu, Ariel Borohovitz, Eihab Ghantous, Philippe Taieb, Yoav Granot, Orit Goldstein, Jonathan Calderón Soriano, Ricardo Rubio-Oliver, Joaquin Ruiz-Rivas, Zeev Zalevsky, Javier Garcia-Monreal, Maxim Shatsky, Sagi Polani, Yaron Arbel

Atrial fibrillation (AF) is a major cause of morbidity and mortality. Current guidelines support performing electrocardiogram (ECG) screenings to spot AF in high-risk patients. The purpose of this study was to validate a new algorithm aimed to identify AF in patients measured with a recent FDA-cleared contact-free optical device.

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Nov 2022

Bio and electronically controlled surface plasmons polaritons generated by coupling between nano-antenna and photosynthetic protein-photosystem I

Itai Carmeli, Ibrahim Tanriover, Tirupathi Malavath, Moshik Cohen, Yossi Abulafia, Olga Girshevitz, Shachar Richter, Koray Aydin, Zeev Zalevsky

Surface plasmons polaritons (SPP) hold great promise for the next generation of fast nanoscale optoelectronic devices, as silicon-based electronic devices approach fundamental speed and scaling limitations. However, in order to fully exploit the potential of plasmonics, devices and material systems capable of actively controlling and manipulating plasmonic response is essential. Here, we demonstrate active control of the electric field distribution of a micro antenna by coupling SPP to a photosynthetic protein with outstanding optoelectronic properties and long range and efficient exciton transfer ability. The hybrid bio-solid state active platform is able to tune and modulate the optical activity of a micro plasmonic antenna via interaction of the bioactive material with plasmon oscillations occurring in the antennae. In addition, we demonstrate that the effect of the coupling can be further enhanced and controlled by an external potential applied to the micro antenna Photosynthetic hybrid system.

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Nov 2022 • Solid State Ionics

Multi-spray pyrolysis for combinatorial synthesis of materials libraries and their high-throughput screening: Application to Li-ion conducting electrolytes

Shay Tirosh, Niv Aloni, David Cahen, Diana Golodnitsky

We present a multi-head spray pyrolysis system and its application in high-throughput combinatorial synthesis for research of solid Li-ion conductors. Each spraying nozzle is fed with a separate precursor solution. The overlap of areas that are sprayed leads to unprecedented composition flexibility of the films obtained after pyrolysis. Thus, a library with a continuous composition spread of a Li-La-P-O model system is formed. The Li-ion conduction was determined on 169 cells of the library, using high throughput impedance measurements in a controlled environment. While the activation energies that were found were relatively small, Li-ion conduction was still low. This low mobility is hypothesized to originate from the sub-optimal occupation of Li sites in the non-stoichiometric materials' lattices, and/or porosity and tortuosity issues, which in turn, reduces their effective concentration and contribution to ion transport. In …

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Nov 2022 • Journal of Virology

Upregulation of ATF4-LAMP3 Axis by ORF45 Facilitates Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus

Qinqin Sun, Fan Wang, Qingyang Chen, Ronit Sarid, Xiaojuan Li, Ersheng Kuang

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a γ-oncogenic herpesvirus, and both lytic and latent infections play important roles in its pathogenesis and tumorigenic properties. Multiple cellular pathways and diverse mediators are hijacked by viral proteins and are used to support KSHV lytic replication. In previous studies, we revealed that KSHV ORF45 promoted KSHV transcription and translation by inducing sustained p90 ribosomal S6 kinase (RSK) activation and the phosphorylation of its substrates c-Fos and eIF4B. However, the cellular mediators required for lytic replication remain largely unknown. Here, we reveal that ORF45 activates eIF2α phosphorylation and ATF4 translation and then upregulates the expression of lysosome-associated membrane protein 3 (LAMP3) in an ATF4-dependent manner during KSHV lytic replication. Consequently, LAMP3 promotes Akt and ERK activation and then …

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Nov 2022 • Crystal Growth & Design

Localized Heating Tailors Nucleation for Reproducible Growth of Thin Halide Perovskite Single Crystals

Sujit Kumar, Alexandra Rukban, Julia Sinisi, Vinayaka H Damle, David Cahen

Halide perovskites (HaPs) are functional semiconductors that can be prepared in a simple, near-room-temperature process. With thin polycrystalline HaP films, excellent solar cells, light-emitting diodes (LEDs), and (also as single crystals) high-energy radiation detectors have been demonstrated. The very low single-crystal defect densities make HaP thin single crystals (TSCs), instead of polycrystalline HaP films an attractive option, to boost device performances and for fundamental research. However, growing TSCs is challenging primarily because of random multiple nucleations, which, in the often-used space-confined geometry, is favored at the substrate boundaries, where loss of organo-amines and solvents occurs. We show that fewer and better-quality thin crystals nucleate and grow reproducibly away from the substrate edges in the substrate center, if we localize the heating (needed for inverse-temperature …

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Nov 2022 • Cell Reports

Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome

Hadar Bootz-Maoz, Ayelet Pearl, Ehud Melzer, Stephen Malnick, Efrat Sharon, Yifat Bennet, Rotem Tsentsarevsky, Shlomi Abuchatzera, Sivan Amidror, Elana Aretz, Shalhevet Azriel, Chen Gam Ze Letova, Maria Naama, Irit Shoval, Orly Yaron, Sarit Karako-Lampert, Shai Bel, Nissan Yissachar


Nov 2022 • Scientific Reports

Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development

Yishay Wineberg, Itamar Kanter, Nissim Ben-Haim, Naomi Pode-Shakked, Efrat Bucris, Tali Hana Bar-Lev, Sarit Oriel, Harel Reinus, Yishai Yehuda, Rotem Gershon, Rachel Shukrun, Dekel Dov Bar-Lev, Achia Urbach, Benjamin Dekel, Tomer Kalisky

Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme—a transient kidney-specific progenitor state—undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms’ tumor that mimics normal kidney development. While human kidney development has been characterized at the gene expression level, a comprehensive characterization of alternative splicing is lacking. Therefore, in this study, we performed RNA sequencing on cell populations representing early, intermediate, and late developmental stages of the human fetal kidney, as well as three blastemal-predominant Wilms’ tumor patient-derived xenografts. Using this newly generated RNAseq data, we identified a set …

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Nov 2022 • Measurement

Opto-mechanical magnetometer based on laser speckle correlation

Vismay Trivedi, Swapnil Mahajan, Mugdha Joglekar, Nirav Joshi, Vani Chhaniwal, Satish Kumar Dubey, Zeev Zalevsky, Bahram Javidi, Arun Anand

Magnetic field sensing plays vital role in vast range of areas such as navigation, military, and biomedical sciences. In recent times, optical sensors have made great advances, resulting in the development of magnetic field sensors based on optical principles due to their non-susceptibility to electromagnetic interference. Here, a simple and inexpensive approach for sensing magnetic field, that converts the magnetic field into a mechanical translation (of the sensing element) and then change into optical signals is presented. These optical signals are speckle patterns generated using a laser beam reflected off an optically rough metal cantilever which is exposed to the magnetic field. Magnetic field is quantified by measuring the changes in the speckle pattern using the intensity correlation technique. The approach can measure the static and time varying magnetic fields. The proposed system has a resolution of 2.2 and can measure magnetic fields with less than a 2% error.

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Nov 2022 • Materials

Phosphate-Trapping Liposomes for Long-Term Management of Hyperphosphatemia

Chen Tzror-Azankot, Adi Anaki, Tamar Sadan, Menachem Motiei, Rachela Popovtzer

Hyperphosphatemia is a typical complication of end-stage renal disease, characterized by elevated and life-threatening serum phosphate levels. Hemodialysis does not enable sufficient clearance of phosphate, due to slow cell-to-plasma kinetics of phosphate ions; moreover, dietary restrictions and conventional treatment with oral phosphate binders have low success rates, together with adverse effects. Here, we developed a new concept of phosphate-trapping liposomes, to improve and prolong the control over serum phosphate levels. We designed liposomes modified with polyethylene glycol and encapsulated with the phosphate binder ferric citrate (FC liposomes). These liposomes were found to trap phosphate ions in their inner core, and thereby lower free phosphate ion concentrations in solution and in serum. The FC liposomes showed higher phosphate binding ability as phosphate concentrations increased. Moreover, these liposomes showed a time-dependent increase in uptake of phosphate, up to 25 h in serum. Thus, our findings demonstrate effective long-term phosphate trapping by FC liposomes, indicating their potential to reduce serum phosphate toxicity and improve current management of hyperphosphatemia.

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Nov 2022 • Kate Atkinson, viii-viii, 2022

Acknowledgements

Armelle Parey

As Kate Atkinson has Effie say in Emotionally Weird, adapting John Donne,‘No woman is an island’(EW 219). Genuine thanks to Paul Clark at Manchester University Press and the anonymous experts and reader for supporting the project. Warm-hearted thanks are due to family, colleagues and friends for their support and notably to Josephine McNamara for her generous encouragement and faith, to Georges Letissier and Isabelle Roblin for their valuable advice, to Andrew Guy and Sandra Robinson for their helpful proof-reading, to James and Jacques McNamara for simply being there.

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Nov 2022 • arXiv preprint arXiv:2211.06278

Temperature-dependence of the CISS effect from measurements in Chiral molecular intercalation super-lattices

Subhajit Sarkar, Seif Alwan, Amos Sharoni, Yonatan Dubi

We detail here some matters arising from the recent paper by Qian et. al., Nature 606, pages 902-908 (2022). We demonstrate, based on data supplied by Qian et. al., and corroborated by theoretical modeling, that one of the central conclusions of the manuscript - namely the behavior of the chirality-induced spin-selectivity (CISS) effect at low temperatures - can actually be consistently interpreted in a different way, which is in fact opposite to the interpretation proposed by Qian et. al.

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Nov 2022 • Physical Review B

Universality and microstrain origin of the ramp reversal memory effect

Elihu Anouchi, Naor Vardi, Yoav Kalcheim, Ivan K Schuller, Amos Sharoni

The recently discovered ramp reversal memory (RRM) is a nonvolatile memory effect observed in correlated oxides with temperature-driven insulator–metal transitions (IMT). It appears as a resistance increase at predefined temperatures that are set or erased by simple heating–cooling (ie, ramp reversal) protocols. Until now RRM was measured for two materials: VO 2 and NdNiO 3. A heuristic model suggests that the RRM is caused by a local transition temperature increase at boundaries of spatially separated metallic and insulating domains during ramp reversal. However, there is no experimental measure of the magnitude of the effect, which is crucial for the development of a theoretical account of the RRM. Here we show that V 2 O 3 also shows RRM, including all related features, highlighting the generality of the effect. Moreover, an analysis of the RRM as an effective (average) increase of the critical …

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Nov 2022 • The Journal of Physical Chemistry C

Nanostructure-free Metal–Dielectric Stacks for Raman Scattering Enhancement and Defect Identification in CVD-Grown Tungsten Disulfide (2H-WS2) Nanosheets

Bharathi Rajeswaran, Rajashree Konar, Sriram Guddala, Tali Sharabani, Eti Teblum, Yaakov Raphael Tischler, Gilbert Daniel Nessim

Low-wavenumber Raman (LWR) spectroscopy determines signatures in structural information and layer-to-layer dependency of transition metal dichalcogenides (TMDCs). It supports proper 2D TMDC analysis and subsequent layer verification. The nondestructive nature and ultrafast detection make LWR measurements imperative for layer variations and defect investigations. Interference-enhanced Raman scattering utilizes a metal–dielectric layer to enhance the Raman signal. This has been used to study graphene, C60, and Te. Here, we investigate using Al/Al2O3 coatings to enhance the LWR scattering of different 2H-WS2 layers and understand the structures of these large-area nanosheets. Phase-pure WS2 is synthesized by CVD, and the layers are exfoliated via ultrasonication at 80 kHz. Layers were drop-casted on Al/Al2O3 coatings of different thicknesses of Al2O3 to study differences in bilayers up to a …

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Nov 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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